Curriculum Vitae
Updated 4/04
Barry R. Lentz
I.BIOGRAPHICAL DATA
A.PERSONAL INFORMATION:
Business Address: 418A Faculty Laboratory Office
Building 231H
Department
of Biochemistry and Biophysics
University
of North Carolina School of Medicine
Chapel
Hill, NC 27514
Business Telephone: Office: (919) 966-5384, Lab: 962-8317,
FAX: 966-2852
E-Mail: uncbrl@med.unc.edu
B.EDUCATION:
Postdoctoral: National Institutes of Health
Postdoctoral Fellow,
Department
of Biochemistry,
University
of Virginia, Charlottesville, VA 22901
Postdoctoral
Mentor: T.E. Thompson
July, 1973
- August, 1975.
Ph.D.: Cornell University,
Ithaca, NY; NIH Trainee
Physical
and Biophysical Chemistry, August 1973.
Thesis: A Structural Model for Liquid Water.
Advisor: H. A. Scheraga, September, 1966 - June, 1973
B.A.: University of
Pennsylvania, Philadelphia, PA;
Chemistry,
May 1966
C.EMPLOYMENT HISTORY:
1996-1999 Faculty Director, UNC
Macromolecular Interactions Facility
1995-present Director, UNC Program in
Molecular & Cellular Biophysics
1988-present Professor of Biochemistry &
Biophysics
418
Faculty Laboratory Office Building
University
of North Carolina at Chapel Hill
School of
Medicine
Chapel
Hill, NC 27599-7260
1981-1988 Associate Professor
1975-1981 Assistant Professor
Jan.-July, 1972 Visiting Scientist with Professor
H.A. Scheraga
Biophysics
Department, Weizmann Institute of Science
Rehovot,
Israel
1965 - 1966 Research Technician, Professor
Phillip George
Department
of Chemistry
University
of Pennsylvania
Philadelphia,
PA 19104
D.SPECIAL HONORS AND AWARDS:
Cum Laude with Honors,
University of Pennsylvania
Phi Beta Kappa
Phi Lambda Upsilon
NSF Predoctoral Trainee,
Cornell University
NIH Postdoctoral Fellow
American Heart Association
Established Investigator; 1979-1984
University of North Carolina
at Chapel Hill Excellence in Teaching Award, 2001 & 2002
Elected Fellow of American
Association for the Advancement of Science, 2001
E.PROFESSIONAL SOCIETIES:
American Chemical Society,
The Calorimetry Conference
American Society for
Biochemistry and Molecular Biology, Biophysical Society
American Association for the
Advancement of Science
II.TEACHING:
A.FORMAL TEACHING; PREVIOUS POSITION:
University of Virginia;
Medical Biochemistry; 100 first year medical students; 3 recitations/wk; one
semester, 1974; assisted Dr. T. E.Thompson.
B.FORMAL TEACHING; PRESENT POSITION
1. Biochemistry
for Dental Hygiene Students (Biochemistry 7D); 50-60 students; 4-5 lectures/wk,
3 two-hour laboratory sessions and 5 two-hour recitations/semester; one
semester/yr 1975-1977.
2. Nutrition
for Dental Hygiene Students (Biochemistry 8D); 50-60 students; 2 lectures/wk;
one semester/yr, 1975-1977.
3. Overview
of Cell Biology for Dental Hygiene Students (Dental Hygiene 51); 50 students; 3
lectures/wk; one-third semester/yr, 1977-1980.
4. Membrane
Biochemistry (Biochemistry 108); 15-25 advanced undergraduate or graduate
students; 3 lectures/wk; one semester/yr, 1977-present; responsibility shared
with Dr. G. Meissner; Dr. Lentz's contribution is currently 10 lectures on
lipid chemistry and the dynamic structure of model and biological membranes.
5. Seminar in
Membrane Structure (Biochemistry 230); 12 advanced graduate students; 2 hrs/wk;
one semester/yr; 1975, 1977, 1979, 1981, 1987, 1989; responsibility shared with
Dr. G. Meissner; participation by Drs. R.Penniall, P. Morell, and A. Erickson.
6. Physical
Biochemistry (Biochemistry 133;144;143); 15 graduate students; 2-3 hrs/wk; one
semester/yr; 1979-1994; responsibility shared with Dr. Jan Hermans; Dr. Lentz's
contribution is 14 lectures in macromolecular structure and applications of
spectroscopy to Biochemistry, alternating in different years between spin
resonance spectroscopy and optical spectroscopy.
7. General
Biochemistry (Biochemistry 100); 150 undergraduate students; 3 hrs/wk; one
semester/yr; 1981, 1982, 8 lectures on lipid metabolism and oxidative
phosphorylation.
8. Graduate
Biochemistry Seminar (Biochemistry 205); 8-10 graduate students; Tutor and
advise two students in the preparation of a seminar and coordinate the visit of
a leading biochemist in the area of this seminar; one semester every other year
1979-present.
9. Experimental
Approaches to Biochemical Research (Biochemistry 206); 8-12 graduate students;
2 hr lecture/demonstration per year; one semester per year, 1982-1989.
10. Biophysics
(144, 145, 146, 147); planned and initiated a four module course as the core of
the Biophysics Program; 1994-present. Series director; 1994-present. Teach two 15 hour modules: Basic Models in
Structural Biology; Macromolecular Spectroscopy
11.
Biophysics
210/211: Biophysics seminar series and student seminar presentations; required
of all students in the UNC Molecular and Cellular Biophysics Program. Course
preceptor and seminar series coordinator, 1995-present.
12.
Biophysics
(150, 151, 152, 153, 154, 155, 156, 157, 158, 159); planned, initiated, and
coordinate this eight module series that offer students introductions to such
biophysical methods as x-ray crystallography, structural NMR, bioinformatics,
molecular dynamics, analytical ultracentrifugation, cell imaging, mass
spectroscopy, etc. Series
director 1998-present.
C. GRADUATE AND POST-DOCTORAL
RESEARCH TRAINING:
1. Current or
past member of the Graduate Committee of twenty-nine students in the
Biochemistry, Clinical Chemistry, Cell Biology, and Chemistry Ph.D. programs.
2. Candidates
for Ph.D. degree currently in training: none
3. M.S.
student trained:
Ms. Gail McIntyre, Biochemistry
Department, received degree, 1989.
4. Ph.D.'s
trained:
Bryant M. Moore, Vice President Shared
Product Development, Medtronic Cardiac Rhythm Management, Minneapolis, MN,
Ph.D. received 1980 from University of North Carolina at Chapel Hill.
Arthur P. Bode, Professor of Clinical
Pathology and Diagnostic Medicine, East Carolina University School of Medicine,
Greenville, NC. Ph.D. received 1982
from University of North Carolina at Chapel Hill.
David A. Barrow, Lab Manager, Center
for Oral and Systemic Disease, UNC-CH; Ph.D. received 1984 from Univ. of North
Carolina at Chapel Hill.
Marcie Jones Hursting, Clinical Science
Consulting, Potomac, MD. Ph.D. received
1985 from University of North Carolina at Chapel Hill.
Roberta A. Parente, Senior Research
Scientist, Ortho Diagnostic Systems (Johnson & Johnson), Raritan, NJ. Ph.D. received 1985 from Univ. of North
Carolina at CH.
Stephen W. Burgess, Vice President, R
& D, Avanti Polar Lipids, Pelham, AL.
Ph.D. received 1990 from the University of North Carolina at Chapel
Hill.
Susan Windes Tendian, was Research
Scientist at Southern Research Institute in Birmingham, AL, currently
unemployed to raise a family; Ph.D. received May 1991 from the University of
North Carolina at Chapel Hill.
Gwyn A. Cutsforth, Research Scientist
in a Triangle biotech firm; Ph.D. received May 1991 from the University of
North Carolina at Chapel Hill.
Gang Pei, Professor and Head, Laboratory
of Cellular Signal Transduction, Shanghai Institute of Cell Biology, Member Academia
Sinica, Vice President of Chinese Society of Cell Biology; Ph.D. received January, 1992 from the
University of North Carolina at Chapel Hill.
Donald Massenburg, Professor of Internal
Medicine, Lutheran Gen. Hosp., Parkridge, IL; Ph.D. received July, 1992 from
the University of North Carolina at Chapel Hill.
Qing Chen, Senior Staff Scientist at Amgen Corp.,
Camarillo, CA; Ph.D. received January, 1996, from Biochemistry & Biophysics
Department, UNC-CH.
5. Research
Associates trained:
Dr. T. E. Jensen (1979 – 1980) Ford
Motor Company, Scientific Research Laboratory, Dearborn, MI 48121.
Dr. Daniel Powers,(March, 1986-
September) 1989 currently a computer applications specialist at Nortel,
Research Triangle Park, NC;.
Dr. Jogin Wu (1988 – 1993) Associate
Director, Clinical Hematology Laboratory, Duke University Medical Center,
Durham, NC.
Dr. Claudia Soodeen (1991-1992; 6
months) Research Scientist, Lederle-Praxis Biologicals.
Dr. Vishwanath Koppaka (1992-1996)
after teaching math and science in a remote part of India for a year, he is
currently a Research Assistant Professor, Dept of Pharmacology, Univ. of
Penna., Philadelphia, PA.
Mr. Zheng Lian-Tsing (1993-1995)
Visiting Scientist, National Laboratory of Biomolecules, Institute of
Biophysics, Academia Sinica, Beijing, PR China. Currently a graduate student in the Biochemistry & Biophysics
Dept, UNC-CH.
Mr. Wu Hua (1993-1995) Visiting
Scientist, Dept. of Biological Science & Biotechnology, Tsinghua Univ.,
Beijing, PR China. Presently at CI
Technology, Inc, Durham, NC
Dr. Wang Jian-Fang (1994–1997)
Currently a Research Scientist at Dade Behring Diagnostics, Newark, DL.
Dr. Mou Banerjee, Research Associate,
Dept of Biochemistry & Biophysics, Univ. of North Carolina at Chapel Hill,
1994-1997. Currently seeking a position
in India.
Dr. Jinkeun Lee (1995–1998) Senior
Scientist, Transave Company, Princeton, NJ.
Dr. Zhai Xin (1996-1998) Independent
consultant and networking engineer, San Jose, CA.
Dr. Kasturi Mukhopadhyay (1996–1997)
Research associate in membrane biology; School of Life Sciences, Jawharlal
Nehru University, New Delhi, India.
Dr. Szusza Lakos (1997–1999) Associate
Professor, Dept. of Biophysics, Medical University of Pecs, Hungary.
Dr. Kervin Evans, (2003-present) Research
Scientist, US Department of Agriculture, National Center for Agricultural
Utilization Research, Peoria, IL.
Dr. Vladimir Malinin (April, 1998 –January, 2001). Scientist at Elan Pharmaceuticals, Inc., Princeton, NJ.
Dr. Emdadul Haque (June, 1998 – present) Research Associate, Dept of Biochemistry & Biophysics, Univ. of North Carolina at Chapel Hill.
Dr. Rinku Ghosh Majumder (April, 1998 – present) Research Associate, Dept of Biochemistry & Biophysics, Univ. of North Carolina at Chapel Hill.
Dr. Gabriel Weinreb (February, 1999 –June 2003) Research Assistant Professor, Dept of Cell & Developmental Biology, Univ. of North Carolina at Chapel Hill.
Dr. JinMing Huang (August, 1999–Sept. 2000) Research Associate, Dept of Chemistry, Wake Forest Univ., Winston Salem, NC.
Dr. Moses Dennison (April, 2001 – present) Research Associate, Dept of Biochemistry & Biophysics, Univ. of North Carolina at Chapel Hill.
D. SPECIAL TEACHING:
1. Honors
Research (Chemistry 99 or Honors 37); supervised undergraduate research of:
Kenneth Morrison, 1977; Randall Davis, 1980-1981; Tamra Carpenter, 1981-1982;
Sherman Madden, 1982; Robert Whitaker, 1985-1986; Mohak Davé, Spring,1994.
2. Supervise
or have supervised laboratory research of several other undergraduate students
with chemistry, biology, or physics majors, 1976-present.
3. Advisor to
a high school student in UNC Summer Research Apprentice Program for minority
students, 1980.
4.
Biochemistry
207. Advanced Biochemistry Laboratory.
Eight graduate students; one-half semester per student; 1975-1997.
5.
Pharmaceutics
163. Advances in Drug Delivery. One lecture per year on the mechanism of
membrane fusion; 1992-present.
6.
Supervised
research and arranged and sponsored a research visit to Beijing Medical
University for Dr. Jeffrey Simko, Ph.D. in analytical chemistry and a medical
student at UNC-CH; fall, 1996, spring & summer, 1997.
III. PROFESSIONAL AND COMMUNITY
SERVICE ACTIVITIES:
A. EXTRA-UNIVERSITY SERVICE:
1. Peer
Review
National Science Foundation Peer Reviewer,
(Biophysics, International Program, Biochemistry,
Physiology).
Peer Reviewer for United States-Israel
Binational Science Foundation
Peer Reviewer for March of Dimes Birth Defects
Foundation
Ad Hoc Member of Molecular and Cellular
Biophysics Study Section of National Institutes
of Health, 1984
Member of a Special Study Section of the
National Institute of Health to review a challenge
to a Molecular and Cellular Biophysics Study Section Review, April, 1985.
National Science Foundation EPSCoR
("Experimental Program to Stimulate Competitive
Research") Panel Member, May, 1986
External reviewer for the Physical Biochemistry
Study Section of National Institutes of
Health, 1987.
National Science Foundation Biophysics Program
Panel Member, July, 1987 - June, 1988
Member of the National Institutes of Health
Biophysics and Biochemistry-B Study Section,
July, 1988 - 1992.
Site-visit review of "Cell Imaging
Laboratory" Special Resource for the NIH, July, 1991.
National Institutes of Health Reviewer
Reserve, July, 1992- June 1996.
NIH Promotion Committee for Dr. Leonid
Chernomordik, 1997.
National Institutes of Health Special Emphasis Panel (Biomedical Research Training), Nov, 1997, site visit to Univ. of Mich., Oct, 1997.
NIH, Special Study Section for NRSA awards, March 23-24, 1998.
2. Professional
Journal Review
Reviewer for Biochemistry, Analytical Biochemistry,
Biophysical Journal, Nature, Archives of Biochemistry and Biophysics, Journal of Biological Chemistry, Journal of Biochemical and Biophysical Methods, and Blood
Editorial Board Member, Journal of Fluorescence, 1992-1998. Managing editor of a special volume on "Fluorescent Methods
for Resolving Microenvironments in Membranes, 1996."
Editorial Board Member, Biophysical Journal, July, 1998-2002.
Associate Editor, Biophysical Journal, June 2002-present.
3. Organization
of Scientific Meetings
Organizer of "Liposomes in Space"
Workshop at the 1986 Biophysical Society Meeting.
Fund-Raising Chairman and Co-Chairman of the
Organizing Committee for "Fundamental
Mechanisms of Membrane Fusion" Symposium held at the
International Biophysics Congress,
Jerusalem, ISRAEL, 1987.
Chair of Session "Formation and Function
of Platelet Micro-particles" at the 9th National Conference on Thrombosis and Hemostasis,
American Heart Association
Meetings, Dallas, 1990.
Organizer of a Symposium on "Protein-Lipid
Interactions and the Stabilization of Membrane
Proteins" at the 1993 Calorimetry Conference held at Duke University, Durham, NC, 7/18/93-7/23/93.
Co-Organizer of "Mechanisms of Biological
Membrane Fusion" satellite symposium held in conjunction with the
International Congress of Pure and Applied Biophysics, August 8-10, 1996,
Noorwijkerhout, The Netherlands.
Chair of the Organizing Committee for
"Membrane Molecular Dynamics", the first International Triangle
Biophysics Symposium jointly sponsored by UNC Molecular & Cellular
Biophysics and Duke Molecular Biophysics Graduate Programs; October 24-26,
1996, Chapel Hill, NC.
Organizer of a joint workshop (Membrane
Structure & Assembly and Biological Fluorescence Subgroups) on
“Applications of Fluorescence Imaging in Cell Membrane Biophysics” at the 1998
Biophysical Society meeting, Kansas City.
Member of the Organizing Committee for the
second International Triangle Biophysics Symposium jointly sponsored by UNC
Molecular & Cellular Biophysics and Duke Molecular Biophysics Graduate
Programs; Nov 19-21, 1998 at the Durham Civic Center) on “Principles of Protein
Design: Theory and Applications.”
Session (“Fusion Techniques
and Mechanisms”) Chair for “Membrane Fusion: Mechanisms and Applications to
Cell Biology, Drug Delivery, and Gene Therapy.” Symposium, Salamanca, Spain,
July 14-18, 1998.
Organizer of “Phospholipases
and Sphingomyelinases: Enzymology at a Surface”, Membrane Structure and
Assembly Subgroup Symposium at the Biophysical Society meeting, New Orleans,
LA, February 12, 2000.
Chair of Organizing
Committee for “Macromolecular Interactions: Emerging Concepts and
Technologies”, the third International Triangle Biophysics Symposium jointly
sponsored by UNC Molecular & Cellular Biophysics and Duke Molecular
Biophysics Graduate Programs; October 19-20, 2000, Chapel Hill, NC.
Symposium organizer 2003
Biophysical Society national meeting: Molecular Mechanisms of Membrane
Fusion: Protein Machines & Lipid Materials
4. Participation
in Professional Societies
Member of the Congressional
Liaison Committee of the Biophysical Society, 1992-present.
Member
of the Advisory Committee of the Membrane Structure and Assembly Subgroup of
the Biophysical Society, 1995-2000.
Chair
of the Membrane Structure and Assembly Subgroup of the Biophysical Society,
1999.
Subgroup
Liaison for the Biophysical Society Administration, 2000.
Elected
Member of the Biophysical Society Council, October, 2001-present.
Chair
of Biophysical Society Minority Affairs Committee, March 2002-present.
5. Consulting
Consultant for American Dade, Miami, FL.,
1983-1987; prethrombotic state.
Consultant for Miles Laboratories, Elkhart,
IN, 1986, 1989; separations of amphipathic compounds.
Consultant for Burroughs-Welcome Research
Laboratories, Research Triangle Park, NC,
1988-1995; fluorescence & DSC studies of reverse transcriptase domain
structure.
Consultant for Ortho Diagnostic Systems,
Raritan, NJ, 1991; liposome technology.
Consultant for Organon Teknika Corporation,
Durham, NC, 1988-1991; surface phenomena in SPIA assays.
6. Current
Community Service
President of the Sunset Beach Taxpayers'
Association representing 1500 property owners in Sunset Beach, NC in dealings
with municipal, state, and federal government representatives and agencies.
Stephen minister and ministerial supervisor at
the University United Methodist Church, Chapel Hill, NC. Stephen ministers are trained Christian
caregivers and supplement the services offered by professional ministerial staff.
President of the Chapel Hill-Carrboro Adult
Soccer Association that has for 30 years organized coeducational, mixed-age and
multi-ethnic-group recreational soccer matches for the Chapel Hill-Carrboro and
surrounding communities.
B. UNIVERSITY SERVICE:
1. Committees
Member of the Dental Hygiene Academic
Performance Committee, 1977-1986.
Member of Search Committee for Director of
Dental Hygiene, 1979-1980.
Program Review Committee of the Graduate
School, 1992-present.
SACS: Member of the Task Force on Graduate
& Professional Programs, 1993-1994.
Chairman of a subcommittee preparing a report
on interdisciplinary studies.
Member of the Acting Dean's Advisory Committee
on the Reorganization of the
Graduate School, Feb, 1995-1996.
Member of three Search Committees to recruit
an Associate and two Assistant Deans of the Graduate School; Spring, 1995.
Member, Agenda Committee of the Faculty
Council, 1997.
Member, Graduate School Committee on Conflict
of Interest, 1997.
Member, Advisory Committee to the Curriculum
in Applied Sciences, 1997-2000.
Member, Director Search Committee, Curriculum
in Applied Science, Spring, 1998.
Member, Biophysics faculty search Committee, Physics Department, January, 2002-present.
Member of the Program Review Committee for the
Physics Department, March, 2002.
2. Contributions
to the Scholarly Community
Organizer and coordinator of UNC-Duke
Biomembrane Structure Club with thirteen faculty participants from the
Biochemistry, Anatomy, and Physiology Departments at both institutions; 1976 -
1996.
Organizer of Coagulation
Journal Club with student and faculty participants from Biochemistry,
Chemistry, Pathology, and Medicine Departments. Focuses on role of platelets in coagulation in general and
specifically on prothrombin and Factor X activation; 1982-1989.
Organized the visit of Dr. F.A. Dombrose of
Organon Teknika Corporation as the N.C. Biotechnology Center Visiting
Industrial Scientist at UNC, Spring, 1987.
Arranged & coordinated the Wellcome
Visiting Professorship of Professor Lin Ke-Chun, Director of the Biophysics
Department of Beijing Medical University, P.R. of China; 2/26/93-3/6/93.
Originator & coordinator
of the Beijing/Chapel Hill Biophysics Exchange Program, funded by The UNESCO
Executive Committee for Molecular and Cell Biology; 1993- present.
Organizer of the Surfaces in Hematology Club
with trainee and faculty participants from five departments at UNC Chapel Hill;
1994-1996.
3. Administration
Elected representative to the UNC faculty
council; 1977-1980; 1994-2000.
Proposed, organized, chaired the planning
committees for, and implemented a Graduate Training Program in Molecular &
Cellular Biophysics at UNC, 12/91- 4/95.
Director of the Program 4/95-present.
Member of the Administrative Board of the
Graduate School, 1992-1998. Chair of a
subcommittee to review student appeals, 1993.
Founder and Faculty Director of the
Macromolecular Interactions Facility that provides to UNC and Research Triangle
area laboratories inter-related biophysical methods used to characterize the
interactions between and solution structure of biological macromolecules. 1996-1999.
C. SCHOOL OF MEDICINE SERVICE:
Sub-committee of Faculty Promotions Committee, 1982.
Faculty Panel to interview candidates for Associate Dean
for Administration; 1985.
Ad hoc steering committee appointed by the Dean of
the School of Medicine to initiate and facilitate discussions between UNC and
Organon-Teknika Corporation on mutual interests in the area of biomedical
research and development, Fall, 1987.
Thrombosis and Hemostasis Advisory Committee, July 1988.
Member, Search Committee for the Physiology Chair,
December 1989 to 1991.
Subcommittee on Graduate Education in Basic Sciences for reaccreditation by the Liaison Committee on Medical Education (LCME), 1996.
Chair of the Faculty Council Nomination Committee for the
School of Medicine, 1997.
Member and Co-Chair of Basic Sciences Review Group,
Post-tenure Review Committee, School of Medicine, 1999-2000.
D. DEPARTMENT OF BIOCHEMISTRY
SERVICE:
1. Committees
Member of the Biochemistry Chairman's
committee to reorganize the graduate curriculum in Biochemistry, 1977.
Chairman of a committee to establish
curriculum and requirements for the Master of Science in Biochemistry, 1977.
Member of the Biochemistry
Chairman's committee to evaluate the physical chemistry requirements of the
Biochemistry Ph.D. degree program; 1978-1983.
Member of the Biochemistry Department Library
Committee, 1978 - present.
Member of the Biochemistry Seminar Program
Committee; 1977 - 1982.
Member of the Biochemistry Graduate
Recruitment and Admissions Committee;
1979 -
1991.
Member of the Biochemistry Equipment
Committee; 1978-1982.
Member of the Biochemistry Graduate Admissions & Advisory Committee; 1985-1995.
Member of the Biochemistry Department Space
Committee; 1986.
Chair of the Biochemistry Department Ad Hoc
Committee on Student Grant Proposal Guidelines; 1987.
Member of the Biochemistry
Department Committee on Joint Appointment Policy; 1987, 1989.
Member of the Biochemistry
Department Committee on Graduate Curriculum Change; 1988.
Member of the Biochemistry
Department Ad Hoc Committee on Revision of Student Grant Proposal Guidelines,
1988.
Member of Biochemistry
Recruitment Committee for a position in Structural Basis of Cooperative
Enzymatic Mechanisms, Nov, 1990 to June, 1991.
Chair of the Graduate Curriculum Review
Committee, 11/91-11/92.
Member of Biochemistry Recruitment Committee
for a position in Structure Determination by NMR, 1992.
Member, Graduate Program Advisory Committee,
1996-1998.
Member of the Biochemistry
Department Ad Hoc Committee on Revision of Student Grant Proposal
Guidelines, 1998; 2000.
Chair of Faculty-recruiting
committee to recruit two biophysicists to the Department of Biochemistry &
Biophysics, September 2001 – April 2002.
2. Administration
Organizer and faculty advisor for the
Biochemistry Student-sponsored Invited Lecturer Program; 1977-1982.
Organizer of weekly luncheons for students and
invited speakers; 1977-1982.
Associate Director of Graduate Studies,
Department of Biochemistry and Nutrition; 1985-1991.
III. RESEARCH
A. MAJOR AREAS OF RESEARCH
INTEREST:
In general, my research has applied the techniques and
concepts of physical chemistry to the solution of biologically relevant
problems. My thesis research involved a
theoretical treatment of the structure of water and aqueous solutions with the
purpose of gaining insight into the effect of water on protein structure. Since completing my formal training, I have
been engaged in experimental studies that aim to determine the molecular basis
for the physical and biological properties of increasingly complex membrane systems. In these studies, I have used fluorescence
spectroscopy, nuclear magnetic resonance spectroscopy, Fourier transform
infrared and CD spectroscopy, microcalorimetry, electron microscopy, enzyme
kinetics, molecular biological protein manipulations, standard biochemical
techniques, and the concepts of statistical thermodynamics to define the
relationship of membrane and protein structure to biological function. My overriding goal has been to apply the
basic principle of molecular structure and dynamics to the solution of
practical problems in the biomedical sciences.
In one project, my laboratory seeks to define the
mechanisms by which platelet-membrane phosphatidylserine (PS) regulates
thrombin formation during blood coagulation.
This project started with studies of membrane morphological and
biochemical changes associated with human platelet stimulation. We were the first to show that PS, which
appears mainly on the cytoplasmic surface of resting platelet membranes,
appears on the plasma-exposed surface of membrane vesicles that derive from
human platelets upon their activation and that these vesicles were needed for
prothrombin activation to thrombin during blood coagulation. Currently, our work focuses on biophysical
studies of the membrane assembly and lipid-regulation of the enzyme-cofactor
complex that activates prothrombin to thrombin. We were the first to report a specific requirement for PS as
opposed to other negatively charged lipids, and we hypothesized that PS might
be a specific regulator of blood coagulation.
We have now shown that PS allosterically up-regulates the enzyme that
activates prothrombin, enhances the ability of the cofactor for this reaction
to bind the enzyme and alters the conformation of the substrate. Thus, PS is the second messenger that turns
on thrombin generation. We have located
two regulatory sites on prothrombin, two on the enzyme, and four on the
cofactor. We have located the two sites
on prothrombin, narrowed the location of the two sites on the enzyme, and located
one of the four sites on the cofactor.
One current effort is to define the lipid specificity of these sites and
ultimately to define the structure of these PS-sensitive regulatory sites. We are also seeking to understand how one or
more of the regulatory sites on the cofactor might be linked to a wide-spread
mutation that is clearly correlated with thrombotic disease.
Another project aims to establish in model membranes the
molecular mechanism by which poly(ethylene glycol) (PEG) induces membrane fusion. We started this work as a means to
understand how PEG facilitated fusion of cell membranes to create hybrid cells,
but have more recently found that PEG-mediated of pure lipid synthetic
membranes is an excellent model for much more complex, protein-mediated
cellular fusion events. We have
proposed an hypothesis that describes the sequence of molecular reorganizations
needed to accomplish fusion of juxtaposed lipid bilayers. This hypothesis accounts for the sequence of
electrical changes observed during fusion between cell compartments as well as
for the large activation energies associated with the cellular fusion
process. As such, it provides strong
evidence that cell membrane fusion is lipidic in its basic mechanism. We are currently examining the details of
this mechanism both to test it experimentally and to explore how proteins might
catalyze the rate-limiting individual steps of the process. We plan to extend the methods we developed
for these studies to examine the mechanism by which the simplest and best
understood cellular fusion machine, the influenza virus protein hemagglutinin,
induces fusion of viral membrane to the endosome membrane during viral
infection. We will also examine the
effect of the basic machinery of exocytotic fusion (the “core complex”) on
fusion of our model membranes.
Ultimately, we hope to use this information to find methods for better
delivering drug-laden liposomes to and inducing their fusion with target cells.
B. GRANTS AWARDED (or
pending for likely funding):
1. Principal
Investigator
a. National
Institutes of Health GM32707-17 to 21
b. "Microstructural
Heterogeneity in Membranes"
c. $210,000
first year
d. 4/1/02
to 3/31/06
e.
30%
effort
2. Principle
Investigator
a. National
Institutes of Health HL072827
b. “Lipid Regulation of Thrombin Generation”
c. $328,526
requested; $275,000 recommended
d. 7/1/04
to 6/30/08; pending approval by Council (20%tile score)
e. 30%
effort
3. Principle
Investigator
a. National
Institutes of Health 1T32GM08570-01
b. "Molecular
and Cellular Biophysics Training Program"
c. 6
positions per year; renewal request for 12 per year
d. 7/1/95
to 6/30/05.
e. 20%
effort
C. PUBLICATIONS:
In Refereed Journals:
1. George P,
Witonsky RJ, Trachtman M, Wu C, Dorwart W, Richman L, Richman W, Shuravh F, Lentz B: An Enquiry into the Importance of Solution
Effects in Phosphate
Ester and Anhydride Reactions. Biochim
Biophys Acta 223:1-15 1970.
2. Lentz BR,
Scheraga HA: Water Molecule
Interactions: Stability of Cyclic Water Polymers. J Chem Phys 58:5296-5308, 1973.
3. Lentz BR,
Hagler AT, Scheraga HA: Structure of
Liquid Water. II. Improved Statistical Thermodynamic Treatment and Implications
of a Cluster Model. J Phys Chem
78:1531-1550, 1974.
4. Lentz BR,
Hagler AT, Scheraga HA: Vibrational
Frequencies of Water Clusters. J
Phys Chem 78:1844-1847, 1974.
5. Lentz BR,
Barenholz Y, Thompson TE: A Simple
Method for the Synthesis of Cholesterol Esters in High Yield. Chem Phys Lipids 15:216-221, 1975.
6. Owicki JC,
Lentz BR, Hagler AT, Scheraga HA:
Structure of Liquid Water.III.
Thermodynamic Properties of Liquid Deuterium Oxide. J Phys Chem
79:2352-2361, 1975.
7. Suurkuusk
J, Lentz BR, Barenholz Y, Biltonen RL, Thompson TE: A Calorimetric and Fluorescent Probe Study of the Gel-Liquid
Crystalline Phase Transition in Small, Single-Lamellar Dipalmitoyl
Phosphatidylcholine Vesicles. Biochemistry
15:1393-1401, 1976.
8. Lentz BR,
Barenholz Y, Thompson TE: Fluorescence
Depolarization Studies of Phase Transitions and Fluidity in Phospholipid
Bilayers, I. Single Component
Phosphatidylcholine Liposomes. Biochemistry
15:4521-4528,1976.
9. Lentz BR,
Barenholz Y, Thompson TE: Fluorescence
Depolarization Studies of Phase Transitions and Fluidity in Phospholipid
Bilayers. II. Two-Component Phosphatidylcholine Liposomes. Biochemistry 15:4529-4537, 1976.
10. Roseman M,
Lentz BR, Sears B, Gibbs D, Thompson TE:
Properties of Sonicated Vesicles of Three Synthetic Phospholipids. Chem Phys Lipids 21:205-222,1978.
11. Shaw JM,
Hutton WC, Lentz BR, Thompson TE:
Proton NMR Study of the Decay of Transbilayer Compositional Asymmetry
Generated by a Phosphatidylcholine Exchange Protein. Biochemistry 16:4156-4163, 1977.
12. Lentz BR,
Freire E, Biltonen RL: Fluorescence and
Calorimetric Studies of Phase Transitions in Phosphatidylcholine Multilayers:
Kinetics of the Pretransition. Biochemistry
17:4475-4480, 1978.
13. Lentz BR,
Litman BJ: Effect of Head Group on
Phospholipid Mixing in Small, Unilamellar Vesicles: Mixtures of Dimyristoyl
Phosphatidylcholine and Dimyristoyl Phosphatidylethanolamine. Biochemistry 17:5537-5543,1978.
14. Moore BM,
Lentz BR, Meissner G: Effects of
Sarcoplasmic Reticulum Ca2+-ATPase on Phospholipid Bilayer Fluidity:
Boundary Lipid. Biochemistry 17:5248-5255, 1978.
15. Lentz BR,
Moore BM, Barrow DA: Light-Scattering
Effects in the Measurement of Membrane Microviscosity with Diphenylhexatriene. Biophysical
J 25:489-494, 1979.
16. Lentz BR,
Alford DR, Dombrose FA: Determination of
Phosphatidylglycerol Asymmetry in Small, Unilamellar Vesicles by Covalent
Labelling. Biochemistry 19:2555-2559, 1980.
17. Barrow DA,
Lentz BR: Large Vesicle Contamination
in Small, Unilamellar Vesicles. Biochim
Biophys Acta 597:92-99, 1980.
18. Lentz BR,
Barrow DA, Hoechli M:
Cholesterol-Phosphatidylcholine Interactions in Multilamellar
Vesicles. Biochemistry
19:1943-1954, 1980.
19. Bode AP,
Dombrose FA, Lentz BR, Roberts HR: The
Platelet Membrane as a Catalytic Surface in Thrombin Generation: Availability
of Platelet Factor 1 and Platelet
Factor 3. N Y Acad Sci
370:348-358, 1981.
20. Barrow DA,
Lentz BR: A Model for the Effect of
Lipid Oxidation on Diphenylhexatriene Fluorescence in Phospholipid Vesicles. Biochim
Biophys Acta 645:17-23, 1981.
21. Dombrose
FA, Bode AP, Lentz BR: Differentiation
of Factor V-like Coagulant Activity from Catalytic Phospholipid-like Surface
Activity in Membrane Fractions Derived from Human Platelets. Thrombosis Research 22:603-621,1981.
22. Lentz BR,
Moore BM, Kirkman C, Meissner G:
Lipid-Protein Interactions in Sarcoplasmic Reticulum: A Disrupted
Secondary Lipid Layer Surrounds the Ca2+-ATPase. Biophysical J 37:30-32, 1982.
23. Moore BM,
Lentz BR, Hoechli M, Meissner G: Effect
of Lipid Membrane Structure on the ATP Hydrolyzing Activity of the
Calcium-Stimulated Adenosine-Triphosphatase of Sarcoplasmic Reticulum. Biochemistry
20:6810-6817, 1981.
24. Lentz BR,
Hoechli M, Barenholz Y: Acyl Chain
Order and Lateral Domain Formation in Mixed Phosphatidylcholine-Sphingomyelin
Multilamellar and Unilamellar Vesicles.
Biochemistry 20:6803-6809, 1981.
25. Lentz BR,
Alford DR, Hoechli M, Dombrose FA:
Phase Behavior of Mixed Phosphatidylglycerol-Phosphatidylcholine
Multilamellar and Unilamellar Vesicles.
Biochemistry 21:4212-4219, 1982.
26. Lentz BR,
Madden S, Alford DR: Trans-Bilayer
Redistribution of Phosphatidylglycerol in Small, Unilamellar Vesicles Induced
by Specific Divalent Cations. Biochemistry
21:6799-6807, 1982.
27. Barrow DA,
Lentz BR: The Use of Isochronal
Reference Standards in Phase and Modulation Fluorescence Lifetime
Measurements. J Biochem Biophys
Meth 7:217-234, 1983.
28. Lentz BR,
Clubb KW, Barrow DA, Meissner G:
Ordered and Disordered Phospholipid Domains Coexist in Membranes
Containing the Calcium Pump Protein of Sarcoplasmic Reticulum. Proc Natl Acad Sci USA 80:2917-2921,
1983.
29. Barrow DA,
Lentz BR: Quinine as a Fluorescence
Lifetime Standard: Conditions for Effectively Homogeneous Decay. Chem Phys Letts 104:163-167, 1984.
30. Parente RA,
Lentz BR: Phase Behavior of Large
Unilamellar Vesicles Composed of Synthetic Phospholipids. Biochemistry
23:2353-2362, 1984.
31. Lentz BR,
Clubb KW, Alford DR, Hoechli M, Meissner G:
Phase Behavior of Membranes Reconstituted from Dipentadecanoyl
Phosphatidylcholine and the Mg2+-dependent, Ca2+-stimulated
Adenosine triphosphatase of Sarcoplasmic Reticulum: Evidence for a Disrupted Lipid Domain Surrounding Protein. Biochemistry
24:433-442, 1985.
32. Parente RA,
Hoechli M, Lentz BR: Morphology and
Phase Behavior of Two Types of Unilamellar Vesicles Prepared from Synthetic
Phosphatidylcholines: A Freeze-Fracture
and Calorimetric Study. Biochem. Biophys. Acta. 812:495-502,1985.
33. Sandberg H,
Bode AP, Dombrose FA, Hoechli M, Lentz BR:
Expression of Coagulant Activity in Human Platelets: Release of
Membranous Vesicles Providing Platelet Factor 1 and Platelet Factor 3. Thrombos. Res. 39:63-79, 1985.
34. Bode AP,
Sandberg H, Dombrose FA, Lentz BR:
Association of Factor V Activity with Membranous Vesicles Released from
Human Platelets: Requirement for Platelet Stimulation. Thrombosis Res. 39:49-61, 1985.
35. Barrow DA,
Lentz BR: Membrane Structural
Domains: Resolution of Heterogeneous
Diphenylhexatriene Fluorescence Using Phase and Modulation Decay
Measurements. Biophys. J.
48:221-234, 1985.
36. Parente RA,
Lentz BR: Advantages and Limitations of
1-palmitoyl-2-(4'-carboxyethyl)-6-diphenyl-trans-1,3,5-hexatriene)-3-sn-phosphatidylcholine
as a Fluorescent Membrane Probe. Biochemistry
24:6178-6185, 1985.
37. Lentz BR,
Alford DR, Jones ME, Dombrose FA:
Calcium-Dependent and Independent Interactions of Prothrombin Fragment
1 with Phosphatidylglycerol/Phosphatidylcholine Unilamellar Vesicles. Biochemistry
24:6997-7005,1985.
38. Jones ME,
Lentz BR, Dombrose FA, Sandberg H:
Comparison of the Abilities of Synthetic and Platelet-Derived Membranes
to Enhance Thrombin Formation. Thrombosis
Res. 39:711-724, 1985.
39. Jones ME,
Griffith MJ, Monroe DM, Roberts HR, Lentz BR:
Comparison of Lipid -Binding and Kinetic Properties of Normal, Variant,
and Gla - Modified Human Factor IX and Factor IXa. Biochemistry 24:8064-8069, 1985.
40. Jones ME,
Lentz BR: Phospholipid Lateral
Organization in Synthetic Membranes as Monitored by Pyrene-Labeled
Phospholipids: Effects of Temperature
and Prothrombin Fragment 1 Binding. Biochemistry
25:567-574, 1986.
41. Parente RA,
Lentz BR: Fusion and Phase Separation
Monitored by Lifetime Changes of a Fluorescent Phospholipid Probe. Biochemistry 25:1021-1026, 1986.
42. Parente RA,
Lentz, BR: Rate and Extent of
Poly(ethylene glycol)-Induced Large Vesicle Fusion Monitored by Bilayer and
Internal Contents Mixing. Biochemistry 25:6678-6688, 1986.
43. Lentz BR,
Carpenter TJ, Alford DR: Spontaneous
Fusion of Phosphatidylcholine Small Unilamellar Vesicles in the Fluid Phase. Biochemistry
26: 5389-5397, 1987.
44. Lentz BR,
Burgess SW: A Dimerization Model for
the Concentration Dependent Photophysical Properties of Diphenylhexatriene and
Its Phospholipid Derivatives: DPHpPC and DPHpPA. Biophysical J. 56:723-733, 1989.
45. Lentz BR,
Whitt NA, Alford DR, Burgess SW, Yates JC, Nir S: The Kinetic Mechanism of Cation Catalyzed Phosphatidylglycerol
Transbilayer Migration Implies Close Contact Between Vesicles as an
Intermediate State. Biochemistry, 28:4575-4580, 1989.
46. Cutsforth
GA, Whitaker RN, Hermans J, Lentz BR: A
New Model to Describe Extrinsic Protein Binding to Phospholipid Membranes of
Varying Composition: Application to Human Prothrombin and Factor X. Biochemistry
28:7453-7459, 1989.
47. Lentz BR,
Hermans J: A New Model to Describe
Extrinsic Protein Binding to Phospholipid Membranes of Varying Composition:
Quantitative Treatment. Biochemistry
28:7459-7461, 1989.
48. Lentz BR: Membrane "Fluidity" as Detected by Diphenylhexatriene
Probes Chem. Phys. Lipids 50:171-190, 1989.
49. Tendian SW,
Lentz BR: Evaluation of Membrane Phase
Behavior as a Tool to Detect Extrinsic Protein-Induced Domain Formation: Binding of Prothrombin to Phosphatidylserine/Phosphatidylcholine
Vesicles. Biochemistry
29:6720-6729, 1990.
50. Pei G,
Baker K, Emfinger SM, Fowlkes DM, Lentz BR:
Expression, Isolation, and Characterization of an Active Site (SER528 ®
ALA) Mutant of Recombinant Prothrombin. J. Biol. Chem. 266,
9598-9604, 1991.
51. Pei G,
Lentz BR: Isolation and
Characterization of Human Meizothrombin in the Presence of Danzylarginine
N-(3-Ethyl-1,5-Pentanediyl)Amide. Blood Coagulation & Fibrinolysis 2,
309-316, 1991.
52. Wu JR,
Lentz, BR: Mechanism of Poly(ethylene glycol)-Induced Lipid Transfer Between
Phosphatidylcholine Large Unilamellar Vesicles: A Fluorescent Probe Study. Biochemistry,
30, 6780-6787, 1991.
53. Burgess SW,
Massenburg D, Yates J, Lentz BR: Poly(ethylene
glycol)-Induced Lipid Mixing but Not Fusion between Synthetic
Phosphatidylcholine Large, Unilamellar Vesicles. Biochemistry 30,
4193-4200, 1991.
54. Wu JR &
Lentz BR: Fourier Transform Infrared Spectroscopic Study of Ca2+-
and
Membrane-Induced Secondary Structural
Changes in Bovine Prothrombin and Prot hrombin
Fragment 1. Biophys. J., 60, 70-80, 1991.
55. Lentz BR,
Wu JR, Sorrentino AM, Carleton JN: Membrane Binding Induces Lipid-Specific
Changes in the Denaturation Profile of Bovine Prothrombin: A Scanning
Calorimetric Study. Biophys. J., 60, 942-951, 1991.
56. Tendian SW,
Lentz BR, Thompson NL: Evidence from Total Internal Reflection Fluorescence
Microscopy for Calcium-Independent Binding of Prothrombin to Negatively
Charged Planar Phospholipid Membranes. Biochemistry, 30,
10992-10999, 1991.
57. Burgess SW,
Wu JR, Swift K, Lentz BR: Determination of the Rate of Rapid Lipid Transfer
Induced by Poly(ethylene glycol) Using the SLM Fourier Transform Phase and
Modulation Spectrofluorometer. J. of Fluorescence, 1, 105-112,
1991.
58. Lentz BR,
McIntyre GF, Parks, DJ, Yates JC, Massenburg D: Bilayer Curvature and Certain
Amphipaths Promote Poly(Ethylene Glycol) Induced Fusion of Dipalmitoylphosphatidylcholine
Unilamellar Vesicles. Biochemistry 31, 2643-2653, 1992.
59. Burgess SW,
McIntosh TJ, Lentz BR: Modulation of Poly(Ethylene Glycol)-Induced Fusion by
Membrane Hydration: Importance of Interbilayer Separation. Biochemistry,
31, 2653-2661, 1992.
60. Pei G, Laue
TM, Aulabaugh A, Fowlkes DM, Lentz BR: Structural Comparisons of Meizothrombin
and Its Precursor Prothrombin in the Presence or Absence of Procoagulant
Membranes. Biochemistry, 31, 6990-6996, 1992.
61. Pei G,
Powers DD, Lentz BR: Specific Contribution of Different Phospholipid Surfaces to the Activation of Prothrombin by
the Fully Assembled Prothrombinase. J. Biol. Chem. 268:
3226-3233, 1993.
62. Powers, DD,
Lentz, BR: Simulation of Prothrombin Proteolysis by the Full Prothrombinase
Assembled on Varied Phospholipid Surfaces. J. Biol. Chem. 268,
3234-3237, 1993.
63. Massenburg,
D, Lentz, BR: Poly(Ethylene glycol)-Induced Fusion and Rupture of
Dipalmitoylphosphatidylcholine Large, Unilamellar Extruded Vesicles. Biochemistry,
32, 9172-9180, 1993.
64. Pearce KH,
Hof M, Lentz BR, Thompson NL: Comparison of the Membrane Binding Kinetics of
Bovine Prothrombin and Its Fragment1. J.
Biol. Chem. 268, 22984-22991, 1993.
65. Lentz, BR:
Use of Fluorescent Probes to Monitor Molecular Order and Motions within
Liposome Bilayers. Chem. Phys. of
Lipids 64: 99-116, 1993.
66. Wu JR &
Lentz BR: Phospholipid-Specific Conformational Changes in Human Prothrombin
upon Binding to Procoagulant Acidic Lipid Membranes. Thrombosis &
Haemostasis, 71, 596-604, 1994.
67. Wu JR &
Lentz BR: A Method for Quantitative Interpretation of Fluorescence Detection of
Poly(ethylene glycol)-Mediated DPHpPC Transfer and Fusion Between Phospholipid
Vesicles in the Dehydrated State. J. of Fluorescence 4, 153-163, 1994.
68. Lentz BR,
Zhou C-M, Wu JR: Phosphatidylserine-Containing Membranes Alter the Thermal
Stability of Prothrombin's Catalytic Domain: A Differential Scanning Calorimetric
Study. Biochemistry 33, 5460-5468, 1994.
69. Lentz BR:
Polymer-Induced Membrane Fusion: Potential Mechanism & Relation to Cell
Fusion Events. Chem. Phys. Lipids, 73, 91-106, 1994.
70. Lentz, BR:
Are Acidic Lipid Domains Induced by Extrinsic Proteins Binding to Membranes? Molecular
Membrane Biol.,12, 65-67, 1995.
71. Lentz BR:
Fluorescent Lifetimes of Diphenylhexatriene-Containing Probes Reflect Local
Probe Concentrations: Application to the Measurement of Membrane Fusion. J.
of Fluorescence 5, 29-38, 1995.
72. Koppaka V.
& Lentz BR: Binding of Bovine Factor Va to Phosphatidylcholine
Membranes. Biophys. J., 70, 2930-2937, 1996.
73. Cutsforth
GA, Koppaka V, Krishnaswamy S, Wu JR, Mann KG, & Lentz BR: Insights into
The Complex Association of Bovine Factor Va with Acidic-Lipid
Containing Synthetic Membranes. Biophys. J., 70, 2938-2949,
1996.
74. Chen Q,
Lord S, & Lentz BR: Construction, Properties, and Specific Fluorescent
Labeling of A Bovine Prothrombin Mutant Engineered with A Free C-Terminal
Cysteine. Protein Engineering, 9, 545-553, 1996.
75. Koppaka, V,
Wang, J-F, Banerjee, M, Lentz, BR: Soluble Phospholipids Enhance Factor Xa-Catalyzed
Prothrombin Activation in Solution. Biochemistry, 35, 7482-7491
1996.
76. Wu, H,
Zheng, L-X, & Lentz, BR: A Slight Asymmetry in the Transbilayer
Distribution of Lysophosphatidylcholine Alters the Surface Properties and
Poly(ethylene glycol)-Mediated Fusion of Dipalmitoylphosphatidylcholine Large
Unilamellar Vesicles. Biochemistry, 35, 12602-12611, 1996.
77. Lentz, BR,
Wu, JR, Zheng, L-X, & Prevrátil, J: The Interfacial Region of
Dipalmitoylphosphatidylcholine Bilayers Is Perturbed by Fusogenic Amphipaths. Biophys.
J., 71, 3302-3310, 1996.
78. Lee
J-K & Lentz BR: A Slight Outer Leaflet Perturbation Promotes PEG-Induced
Fusion of Lipid Vesicles. Biochemistry, 36, 421-431, 1997.
79. Lentz,
BR, Talbot, W, Lee, J-K, & Zheng, L-X: Transbilayer Lipid Redistribution
Accompanies Poly(ethylene glycol) Treatment of Model Membranes but Is Not
Induced by Fusion. Biochemistry, 36, 2076-2083, 1997.
80. Chen,
Q, Lord, ST, & Lentz, BR: Partially Purified Echis Carinatus Venom Cleaves
Active-Site-Mutated Bovine Prothrombin at Two Sites. Thrombosis Research,
85, 369-375, 1997.
81. Talbot,
W, Zheng, L-X, & Lentz, BR: Acyl Chain Unsaturation and Vesicle Curvature
Alter Outer Leaflet Packing and Promote Poly(ethylene glycol)-Mediated Membrane
Fusion. Biochemistry,36, 5827-5836, 1997.
82. Chen,
Q & Lentz, BR: A Fluorescence Resonance Energy Transfer Study of Shape
Changes in Membrane-Bound Bovine Prothrombin and Meizothrombin. Biochemistry,
36, 4701-4711, 1997.
83. Lee, J-K
& Lentz, BR: Evolution of Lipidic Structures During Model Membrane Fusion
and The Relation of This Process to Cell Membrane Fusion. Biochemistry 36,
6251-6259, 1997.
84. Koppaka, V,
Talbot, WF, Zhai, X., & Lentz, BR: Roles of Factor Va Heavy and
Light Chains in Protein and Lipid Rearrangements Associated with the Formation
of A Bovine Factor Va - Membrane Complex. Biophysical J. 72,
2638-2652, 1997.
85. Harper, MF,
Hayes, PM, Lentz, BR, & Roubey, RAS: Characterization of b2-Glycoprotein I Binding to Phospholipid Membranes. Thrombosis & Haemostasis, 80,
610-614, 1998.
86.
Lee,
JK & Lentz, BR: Secretory and Viral Fusion May Share Mechanistic Events
with Fusion between Curved Lipid Bilayers. Proc. Natl. Acad. Sci. USA, 95,
9274-9279, 1998.
87. Kim, SW,
Ortel, TL, Quinn-Allen, MA, Yoo, L, Worfolk, L, Zhai, X, Lentz, BR, and Kane,
WH: Partial glycosylation at asparagine-2181 of the second C-type domain of
human factor V modulates assembly of the prothrombinase complex. Biochemistry,
38, 11448-11454, 1999.
88. Lentz, BR & Lee, JK: Poly(ethylene
glycol) (PEG)-Mediated Fusion between Pure Lipid Bilayers: A Mechanism in
Common with Viral Fusion and Secretory Vesicle Release? A Review. Membrane Molecular Biology, 16, 279-296, 1999.
89. Lentz, BR: Commentary: Lipids and liposomes
can do more than carry drugs; Phosphatidylserine as a regulator of blood
coagulation. Journal of Liposome
Research, 9, IX-XV, 1999.
90.
Lentz,
BR, Malinin, V, Haque, MdE, and Evans, K: Protein Machines and Lipid
Assemblies: Currents Views of Cell Membrane Fusion. Current Opinions in Structural Biology, 10,
607-615, 2000.
91. Haque , MdE, McIntosh, TJ, Lentz, BR
Influence of Lipid Composition on Physical Properties and PEG-mediated Fusion
of Curved and Uncurved Model Membrane Vesicles: “Nature’s Own” Fusogenic Lipid
Bilayer. Biochemistry, 40,
4340-4348, 2001.
92. Malinin, VS, Haque, MdE Lentz,
BR: The Rate of Lipid Transfer During Fusion Depends on the Structure of
Fluorescent Lipid Probes: A New Chain-Labeled Lipid Transfer Probe Pair. Biochemistry, 40, 8292-8299,
2001.
93. Srivastava,
A, Quinn-Allen, MA, Kim, SW, Kane, WH, Lentz, BR: Soluble Phosphatidylserine (C6PS) Binds to a
Single Identified Site in the C2-Domain of Human Factor Va. Biochemistry, 40, 8246-8255, 2001.
94. Presnell, SR, Tripathy, A, Lentz, BR,
Jin, D-J, Stafford, DW: A Novel Fluorescence Assay To Study Propeptide
Interaction with g-Glutamyl Carboxylase. Biochemistry, 40, 11723-11733,
2001.
95. Haque,
ME, McCoy, AJ, Glenn, J, Lee, JK, Lentz, BR: Effects of Hemagglutinin “Fusion
Peptide” on Poly(ethylene glycol)-Mediated Fusion of Phosphatidylcholine
Vesicles. Biochemistry, 40,
14243-14251, 2001.
96. Wu, JR, Zhou, C-M, Majumder,
R, Powers, DD, Weinreb, G, Lentz, BR: Role
Of Procoagulant Lipids In Human Prothrombin Activation. 1: Prothrombin
Activation By Factor Xa In The Absence Of Factor Va And
In The Absence And Presence Membranes. Biochemistry,
41, 935-949, 2002.
97. Banerjee, M, Majumder, R,
Weinreb, G, Wang, J-F, Lentz, BR: Role
Of Procoagulant Lipids In Human Prothrombin Activation. 2: Soluble Phosphatidylserine Up-Regulates
And Directs Factor Xa To Appropriate Peptide Bonds In
Prothrombin. Biochemistry, 41,
950-957, 2002.
98. Srivastava,
A, Wang, J-F, Rezaie, AR, Stenflo, J, Esmon, CT, Lentz, BR: Localization
of Phosphatidylserine (C6PS) Binding Sites to Structural Domains of
Factor Xa. J. Biol. Chem., 277,
1855-1863, 2002.
99. Malinin,
VS, Frederik, P, Lentz, BR: Osmotic and Curvature Stress
Affect PEG-Induced Fusion of Lipid Vesicles but Not Mixing of Their Lipids. Biophys.
J. 82, 2090-2100, 2002.
100. Malinin,
V.S. & Lentz, B.R.: Pyrene-Cholesterol Reports
The Transient Appearance Of Non-Lamellar Intermediate Structures During Fusion
Of Model Membranes. Biochemistry, 41, 5913-5919, 2002.
101. Zhai, X, Srivastava, A,
Drummond, DC,
Daleke, D, Lentz, BR: Phosphatidylserine
binding alters the conformation and specifically enhances the cofactor activity
of bovine factor Va. Biochemistry, 41, 5675-5684,
2002.
102. Banerjee, M,
Drummond, DC, Srivastava, A, Daleke D, and Lentz BR: Specificity of Soluble Phospholipid Binding Sites on Human Factor Xa. Biochemistry, 41, 2751-62,
2002.
103. Majumder,
R, Weinreb, G, Zhai, Z, Lentz, BR: Soluble Phosphatidylserine Triggers Assembly
in Solution of A Prothrombin-Activating Complex in The Absence of A Membrane
Surface. Journal of Biological Chemistry, 277, 29765-29773,
2002.
104. Haque, MdE and Lentz, BR:
Influence of gp41 Fusion Peptide on the kinetics of Poly(ethylene
glycol)-Mediated Model Membrane Fusion. Biochemistry, 41, 10866-10876,
2002.
105. Evans, KO & BR: Kinetics
of Lipid Rearrangements during Poly(ethylene glycol)-Mediated Fusion of Highly
Curved Unilamellar Vesicles. Biochemistry, 41, 1241-1249, 2002.
106. Majumder R, Wang, F-F,
Lentz, BR: Effects of Water
Soluble Phosphatidylserine on Bovine Factor Xa: Functional and Structural Changes Plus
Dimerization. Biophysical Journal, 84, 1238-1251, 2003.
107. Dennison,
SM, Greenfield, N, Lenard, J, Lentz, BR: VSV Transmembrane Domain (TMD) Peptide Promotes PEG-Mediated Fusion of
Liposomes in a Conformationally Sensitive Fashion. Biochemistry, 41, 14925-14934,
2002.
108. Weinreb, G, Mukhopadhyay, K,
Majumder, R, Lentz, BR: Cooperative
Roles of Factor Va and PS-Containing Membranes as Cofactors in
Prothrombin Activation. Journal of Biological Chemistry, 278, 5679-5684, 2003.
109. Malinin, VS and Lentz, BR: Energetics of Vesicle
Fusion Intermediates: Comparison of Calculations with Observed Effects of
Osmotic and Curvature Stresses. Biophysical Journal, 86, 3951-3964,
2004.
110. Malinin,
VS and Lentz, BR: On
the Analysis of Elastic Deformations in Hexagonal Phases. Biophysical
Journal, 86, 3324-3328, 2004.
111. Haque, MdE and Lentz, BR: Roles of Curvature and Hydrophobic Interstice Energy in Fusion: Studies of Lipid Perturbant Effects. Biochemistry, 43, 3507-3517, 2004.
Patents:
1. Lentz, BR, Majumder, R, Huang, JM: Soluble Phospholipids for Use in Clotting Factor
Assays.
September 2003, US Preliminary Patent No. 5470-398PR
In Textbooks and Review
Volumes:
1. Thompson
TE, Lentz BR, Barenholz Y: A
Calorimetric and Fluorescent Probe Study of Phase Transitions in
Phosphatidylcholine Liposomes. In
"Biochemistry of Membrane Transport" [ed] G. Semenza and E.
Carafoli, Springer-Verlag, Heidelberg, 47-71, 1977.
2. Lentz
BR: Membrane "Fluidity" from
Fluorescence Anisotropy Measurements.
In "Spectroscopic Membrane Probes" [ed] L.M. Loew, Vol.
I, CRC Press, Inc, Boca Raton, FL, 1988, Chapter 2, pp. 13-41.
3. Lentz
BR: Organization of Membrane Lipids by
Intrinsic Membrane Proteins. In
"Advances in Membrane Fluidity" [ed] R.C. Aloia, C.C. Curtain, L.M.
Gordon, Alan R. Liss, Inc., New York, NY, 1988, 141-161.
4. Lentz BR,
Burgess SW, Gratton E: Concentration
Dependence of DPHpPC Lifetime: Photophysics and Utility for Monitoring Membrane
Fusion. In "Molecular Mechanisms
of Membrane Fusion" [ed] S. Ohki, D. Doyle, T. Flanagan, S.W. Hui and
E. Mayhew, Plenum Publishing Corp., New York, 1988, pp. 557-566.
5. Lentz, BR
& Burgess, SW: Fluorescence Lifetime Measurements to Monitor Membrane
Lipid Mixing. Meth. Enzymology, 1993, Vol. 220, Academic Press, Inc.,
NY, pp 42-50.
6. Lentz BR:
Liposomes as a Tool to Study Blood Coagulation. in "Nonmedical Applications
of Liposomes, Volume II" [ed] Y. Barenholz & D.D. Lasic, CRC Press,
Boca Raton, FL, 1995, pp 123-136.
7. Lentz BR,
Siegel D, Malinin V: Filling Potholes on the Path to Fusion. Biophysical Journal, 82, 2002,
555-557.
8. Lentz BR: Exposure of platelet
membrane phosphatidylserine regulates blood coagulation. Progress in Lipid Research, 42 2003,
423-438.
Abstracts (most recent unpublished
work only; these are all represented by manuscripts in some stage of
preparation):
81. Banerjee,
M, Koppaka, V., Zhou, C-M & Lentz, BR: Phosphatidylserine Binding Sites in
Krigle Modules Regulate The Domain Organization and Conformation of Bovine
Prothrombin. Biophyical J. 72: A307, 1997.
82. Wang, J-F, Chen, Q & Lentz, BR: A Fluorescence Resonance
Energy Transfer Study of Prothrombinase Assembly on Phosphatidylserine-Containing
Membranes. Biophysical J 72: A307, 1997.
85. Banerjee, M, Koppaka, V, Zhou, C-M, & Lentz, BR.
Phosphatidylserine Binding Sites in Kringle Modules Regulate the Domain
Organization and Conformation of Bovine Prthrombin. Thrombosis &
Haemostasis, 1997.
86. Wang, J-F, Chen, Q, & Lentz, BR. A Fluorescence Resonance
Transfer Study of Prothrombinase Assembly on PS-Containing Membranes. Thrombosis
& Haemostasis, 1997.
103. Weinreb G. & Lentz, B.R. A Model to Predict the Dependence of
Prothrombin Activation Kinetics on Lipid Concentration and Membrane
Phosphatidylserine Content. Biophysical J. 78, A2466.
105. Haque, E, Koppaka, V, Axelsen, PH, Lentz, BR: Relation between
Bilayer Properties and Structures of HA and HIV Fusion Peptide-Membrane
Complexes. Biophysical J. 82, 2002, A2640.
107. Dennison, M, Bowen, M, Brunger, A, Lentz, BR: SNARE Proteins
Alter Poly(ethylene glycol) (PEG)-Mediated Fusion of Model Membranes. Biophysical
J. 84, 2003, A951.
108. Majumder, R, Quinn-Allen, MA, Kane, WH, Lentz, BR: A
Phosphatidylserine Binding Site Distinct from the C2 Domain Membrane
Attachement Site Regulates the Assembly and Activity of the Human
Prothrombinase. J. of Thrombosis & Haemostasis 1, 2004, Ap1048.
110. Dennison, M & Lentz, BR: Effect of Free Ca2+ on the PEG-Mediated Fusion
of Liposomes Having Synaptic-Vesicle-Like Composition. Biophysical J. 86,
2004, A230.
111. Weinreb, G. & Lentz, BR: Kintetic Model of PEG-Mediate
Vesicle Fusion. Biophysical J. 86,
2004, A231.
D. CURRENT RESEARCH COLLABORATORS:
Dr. Peter Frederik, Pathology Department, University of
Masstricht, The Netherlands, Drs. Frederik and Lentz share an interest in the
molecular mechanism of cell membrane fusion and are exploring ways to
visualize this process using freeze fracture electron microscopy.
Dr. David Daleke, Department of Chemistry, Indiana
University, Bloomington, IN. Dr. Daleke is synthesizing short chain forms of
phosphatidylserine analogues be used by Dr. Lentz's laboratory in screening for
the specificities of regulatory sites on factor Xa and its cofactor,
factor Va. The hope is also
to find compounds that will block prothrombin activation.
Dr. Johan Stenflo, Clinical Chemistry Department, Univ. of
Lund, Malmö General Hospital, Malmö Sweden. Dr. Stenflo is supplying Dr. Lentz’s
laboratory with selected fragments of factor Xa for efforts to
locate the allosteric PS binding site in this serine protease. A three way collaboration is also underway
with Professors Torbjörn Drakenberg and Sture Forsén of the Physical Chemistry
Center of Lund University to determine the structure of the PS-occupied site.
Dr. Brian Edwards, Dept. of Biochemistry, Wayne State
Univ., Detroit, MI. Dr. Lentz’s
laboratory is supplying Dr. Edwards with a peptide fragment containing the PS
regulatory site from prothrombin.
Together, they are trying to obtain crystals of this peptide with and
without co-crystallized PS, and are now trying to make heavy atom derivatives
to assist in structure determination.
Dr. William Kane, Hematology
Division, Duke University School of Medicine, Durham, NC. Drs. Kane and Lentz
are working together to locate and characterize the PS regulatory sites in
blood coagulation factor Va, a critical component of the prothrombin
activating complex. A combination of
mutational, enzymatic, and structural methods are being applied.
Dr. Andreas Holzenburg, Lecturer in
Structural Molecular Biology at the University of Leeds, School of Biochemistry
& Molecular Biology, Leeds, UK.
Drs. Holzenburg, Stoylova (an Associate in Holzenburg’s laboratory), and
Lentz are trying to locate conditions for obtaining 2D crystals of
prothrombinase components on supported bilayers. These will be used to obtained low resolution structures by X-ray
and electron scattering methods. Dr.
Lentz is providing proteins and suggestions for crystalization conditions.
Drs. Ronald Bach (Minneapolis VA Medical Center) and Yale Nemerson (Mt Sinai School of Medicine,
NY, NY). This collaboration will test
the hypothesis that PS regulates the initiation of blood coagulation via the activation of factor Xa
by regulating the dimerization state of tissue factor, an essential cofactor in
this reaction. Drs. Bach and Nemerson
are supplying the tissue factor protein and their expertise in this reaction,
while Dr. Lentz’s group is doing physical studies.
E. SELECTED INVITED RESEARCH
TALKS:
"Structural Basis of PEG-Mediated Membrane
Fusion", National Laboratory of Biomolecules, Institute of Biophysics,
Academia Sinica, Beijing, P.R. China, November 6, 1992.
"Platelet Membranes & Control of Blood
Coagulation", Dept. of Biophysics, Beijing Medical University, Beijing,
P.R. China, November 7, 1992.
"Platelet Membranes & Control of Blood
Coagulation", International Workshop on Biomacromolecules: Structure and
Function, Wuxi, P.R. China, November 12-14, 1992.
"Membrane Structure & Dynamics: A View of Polymer
Induced Membrane Fusion", First Workshop on Physics of Complex Fluids
& Biological Systems, Pohang Institute of Science and Technology (POSTECH),
Pohang, Korea, March 24-26, 1993.
"Platelet Membranes & Control of Blood
Coagulation", POSTECH Life Science Department, Pohang, Korea, 3/23/93.
"Platelet Membranes & Control of Blood
Coagulation", Dept. of Chemistry, Seoul National Univ., Seoul, Korea, 3/27/93.
"Measurement of Membrane Fusion Using Fluorescent
Probes", Plenary lecture presented at The Third Conference on Methods and
Application of Fluorescence Spectroscopy, Prague, Czech Republic, October,
1993.
"Platelet Membranes and Control of Blood Coagulation",
Biochemistry Dept., Cardiovascular Research Institute, Univ. of Limburg,
Maastricht, The Netherlands, October, 1993.
"The Role of Platelet Membranes in Prothrombin
Activation to Thrombin During Blood Coagulation", Univ. of Virginia,
Department of Biochemistry, Charlottesville, VA, 2/17/94.
"Are Acidic Lipid Domains Induced by Prothrombin
Binding to Membranes?" Fogarty Conference on "Domain Organization in
Membranes", NIH, Bethesda, MD, 3/2/94 - 3/4/94.
"Platelet Phosphatidylserine Is An Allosteric
Effector of Prothrombin Activation During Blood Coagulation", Ortho
Diagnostic Systems, Inc., Raritan, NJ, 7/25/95.
“Driving Force and Sequence of Events in PRG-Mediated
Fusion of Phospholipid Vesicles”, "Mechanisms of Biological Membrane Fusion"
satellite symposium held in conjunction with the International Congress of Pure
and Applied Biophysics, August 8-10, 1996, Noorwijkerhout, The Netherlands.
“Allosteric Regulation of Prothrombin Activation by
Phosphatidylserine During Blood Coagulation.”
Univ. of Missouri School of Biological Science, Kansas City, MO,
10/31/96.
“PEG-Mediated Membrane Fusion: Driving Force, Sequence of
Events, and Relationship to Viral or Exocytotic Fusion.” Univ. of Virginia Molecular Biophysics
Seminar, Charlottesville, VA, 11/11/96.
“Allosteric Regulation of Prothrombin Activation by
Platelet Membrane Phosphatidylserine.”
1] Temple Univ. Biochemistry Dept., 12/13/96.
2] Univ. of Pennsylvania
Vascular Biology Series, 12/12/96.
3] Thomas Jefferson Univ.
Cardeza Foundation for Hematologic Research, 12/11/96, Philadelphia, PA.
“PEG-Mediated Model Membrane Fusion: Structural Events and
Their Relation to Events During Biomembrane Fusion.” Dept. Cell Biology & Anatomy, UNC School of Medicine, Chapel
Hill, NC, 2/12/97.
“PEG-Mediated Model Membrane
Fusion: Structural Events and Their Relation to Events During Biomembrane
Fusion.” Laboratory for Theoretical
Biology, National Cancer Institute, NIH, Bethesda, MD, 2/19/97.
“The Roles of Phospholipid
in the Functioning of Vitamin K-Dependent Proteins.” FASEB Summer Conference on Vitamin K, Saxtons River, VT,
8/2/97-8/7/97.
“Platelet Membrane Phosphatidylserine as a Second Messenger and Allosteric Regulator of Blood Coagulation.” Dept. of Biochemistry, Molecular & Cell Biology, Univ. of Kansas, Lawrence, KA, Sept. 26, 1997.
“Effects of Fusion Peptide on PEG-Mediated Vesicle
Fusion.” Symposium honoring Prof. T.E. Thompson, Univ. of Virginia,
Charlottesville, Virginia, Nov. 6-7, 1997.
“Platelet Membrane Phosphatidylserine as a Second
Messenger and Allosteric Regulator of Blood Coagulation.” Clinical Chemistry Dept. and Physical
Chemistry Division of the Chemical Center, Univ. of Lund and Malmö, Sweeden,
Nov. 17 & 18, 1997.
“Platelet Membrane Phosphatidylserine as a Second
Messenger and Allosteric Regulator of Blood Coagulation.” Biochemistry
Department, Wayne State University, Detroit, MI, May 19, 1998.
“Fusion between Pure Lipid Bilayers: A Mechanism in Common
with Viral and Exocytotic Fusion.”
“Membrane Fusion: Mechanisms and Applications to Cell Biology, Drug
Delivery, and Gene Therapy.” Symposium, Salamanca, Spain, July 14-18, 1998.
“Peg-Mediated Fusion Between
Pure Lipid Bilayers: Proposed Mechanism, Role Of PEG, Relation To Biomembrane
Fusion.” The Society for Physical Regulation in Biology and Medicine, “Cell
Membrane Sealing and Fusion” Symposium.
Long Beach CA, November 12, 1998.
“Platelet Phosphatidylserine (PS) Is an Allosteric Regulator of Factors Xa and Va And a Key Second Messenger During Blood Coagulation.” February 13, 1999. Membrane Structure and Assembly Subgroup Symposium, Biophysical Society Meeting, Baltimore, MD.
“PEG-mediated lipid bilayer fusion: Steps in common with viral fusion and secretory vesicle release.” April 23, 1999. Molecular Biophysics & Biochemistry Dept., Yale Univ., New Haven, CT.
“PEG-mediated lipid bilayer fusion: A Mechanism in common with secretory and viral fusion.” Materials Research Society Annual Meeting, Nov. 30, 1999, Boston, MA.
“Research At The
Interface Between The Biomedical Sciences And Physics, Chemistry, Mathematics.”
Presented to RISE/MBRS Program students and faculty, Cayey University College,
Cayey, Puerto Rico, March 30, 2000.
“A View of Cell Membrane Fusion: Protein Machines
Work on Lipid Materials.” FASEB Summer Conference on Molecular Biophysics of
Cellular Membranes. Saxtons River, VT,
July 15-20, 2000.
“Poly(ethylene glycol)-Mediated Vesicle Fusion: A
Mechanism in Common with Exocytotic and Viral Fusion.” Presented at a Juan
March Institute international workshop on “Comparison of the mechanisms of
cellular vesicle and viral membrane fusion”, Madrid, November 26- 29,
2000.
“Mechanism of Membrane
Fusion: Protein Machines Work on Lipid Structures.” Presented at Sixth Annual
Life and Physical Science Research Symposium, North Carolina A&T
University, Greensboro, NC, 2/23/01.
“Protein machines and Lipid Assemblies: Current
Views of Cell Membrane Fusion.” Department of Biochemistry, North Carolina
State University, Raleigh, NC, 3/22/01.
“Regulation of Vitamin K Protein Function by
Phospholipid.” FASEB Conference, Saxtons River, VT, August 4-9, 2001.
“Filling the Potholes on the Road to Fusion.” Dept.
of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscatawy,
NJ, February 18, 2002.
“Effects of Fusion Proteins on the Kinetics of Model
Membrane Fusion.” Symposium talk, 2002 Biophysical Society Meeting in San
Antonio, TX.
“Mechanism of Membrane Fusion: Protein Machines Work
on Lipid Structures.” Morgan State University Biomedical Research Seminar
Series, March 13, 2003, Baltimore MD.
“Efficient Human Thrombin Generation Requires
Molecular Phosphatidylserine and Not a Membrane Surface.” July 17, 3003, ICTH
Meeting in Manchester UK.
“How Might Proteins Drive Fusion? Filling Potholes on the Path to Fusion.” Chemistry
Department, Univ. of Maryland, Baltimore Co., November 18, 2003, Baltimore MD.
“Phosphatidylserine: A Second
Messenger in Regulating Blood Coagulation” Chemistry Department, University of
North Carolina at Chapel Hill, November 5, 2003.