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Associate Director,
California NanoSystems Institute
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Professor,
Biological Chemistry | |
Senior Associate Dean of Research,
David Geffen School of Medicine at UCLA
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Director for Strategic Planning and Partnerships,
Jonsson Comprehensive Cancer Center
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Member,
ACCESS Program: Dept. of Biological Chemistry,
Brain Research Institute
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Education: |
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Degrees:
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Ph.D., University of Michigan, Ann Arbor, Michigan, 1975
M.S., University of Michigan, Ann Arbor, Michigan, 1973
B.S., University of Michigan, Ann Arbor, Michigan, 1971
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Honors and Awards: |
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American Cancer Society, Faculty Research Award (1983-1988)
California State Univeristy, Northridge, CSU Chem Club Distinguished Lecturer 1998
March of Dimes, Basil O'Connor Grant (1981-1983)
NIH, Predoctoral Fellow (1972-1975)
NIH, Staff Fellow (1976-1979)
UCLA School of Medicine, Excellence in Education (1991)
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Certifications: |
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Professional Societies:
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American Association for Cancer Research
American Association for the Advancement of Science
American Society for Biochemistry & Molecular Biology
American Society for Cell Biology
American Society for Neurochemistry
Association of American Medical Colleges (AAMC)
GRAND Steering Committee (1998-present) (Chair 2005-present)
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Contact Information:
| Laboratory Address: |
Lab Office
350A BSRB
Los Angeles, CA 90095
UNITED STATES
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| Mailing Address: |
Office
12-138 CHS
CAMPUS - 172216
Los Angeles, CA 90095
UNITED STATES
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| Work Address: |
Laboratory
350 BSRB
Los Angeles, CA 90095
UNITED STATES
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Work Phone Number:
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(310) 825-8680
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Research Interests:
Engineering of a naturally occurring cellular structure
We are using molecular engineering of a naturally occurring cellular structure called a vault to develop a flexible, targetable nano-scale capsule.
Vaults are abundant cellular particles of unknown function found in nearly all eukaryotes (cells containing a nucleus). Cryo-electron microscopy combined with single particle reconstruction has provided overall dimensions of the vault at 42 x 75 nanometers (a nanometer is a millionth of a meter). These measurements indicate that the vault is larger in mass and size than many viruses. The overall structure of the intact vault is like a hollow barrel with two protruding caps and an indented waist with a very thin shell surrounding an internal cavity large enough to encompass several hundred proteins. Thus, the vault particle is a nanocapsule with incredible potential for compound encapsulation, protection, and delivery.
Using a well-characterized insect virus into which a cloned gene can be easily inserted, it is possible to produce large quantities of a given protein in cultured insect cells. We have collaborated with a number of groups to use this system to produce large quantities of the major vault protein (MVP). Interestingly, the protein is able to self-assemble into vault-like particles. These MVP-only vaults are somewhat irregular, often containing distorted caps. However, we have demonstrated that co-production of all three vault proteins (MVP, TEP1 and VPARP) in insect cells results in self-assembly of particles that appear identical to naturally occurring vaults.
By using molecular genetic techniques to modify the gene encoding the major vault protein, vault proteins have been produced with chemically active peptides attached to their sequence. These modified proteins are incorporated into the inside of the vault particle without altering its basic structure. We propose to produce modified vault particles in order to test the concept that vaults can be bioengineered to allow their use in a wide variety of biological applications including drug delivery, biological sensors, enzyme delivery, controlled release, and eventually as parts for nano-electrical machines.
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Technical Research Interest:
We are interested in the biogenesis and function of subcellular
organelles. We have been concentrating on novel cytosolic
ribonucleoprotein particles (RNPs) called vaults. Vaults were
discovered in our laboratory and found to exist in most eukaryotic
cells. They have an intricate shape composed of multiple
arches reminiscent of cathedral vaults, hence their name. Vault
size (~74 x 42 x42 nm), shape and localization suggests that
they may be involved in nucleo-cytoplasmic transport.
We are interested in elucidating the function of these unique
structures and in manipulating their structure to give them new
functions. We are using the baculovirus expression system to
produce recombinant vaults in order to test the concept that
vaults can have a broad nanosystems application as malleable
nanocapsules. Toward this aim we are currently designing particles
with encapsulated fluorescent probes and enzymatically
active protein domains. In addition, a number of strategies are currently being considered to encapsulate chemically active
small molecules into the vault particle. If successful, these
vault nanocapsules can be bioengineered to allow their use in
a wide variety of biological applications including drug delivery,
biological sensors, enzyme delivery, controlled release, and
nano-electrical machine (NEMS) application.
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Additional Information:
Leonard H. Rome is a cell biologist and biochemist who has served on the UCLA School of Medicine faculty since he joined the Department of Biological Chemistry in 1979. He became a full professor in 1988 and has been Senior Associate Dean for Research in the School of Medicine since 1997. Dr. Rome earned his B.S. in Chemistry and M.S. and Ph.D. in Biological Chemistry at the University of Michigan, Ann Arbor. He was a postdoctoral fellow at the National Institutes of Health, where he worked on lysosome biogenesis. Dr. Rome has chaired the School of Medicine Faculty Executive Committee and is actively involved in graduate and medical education. He is a recipient of the School of Medicine Award for Excellence in Education. Since becoming Senior Associate Dean for Research, he has organized a strategic plan for research in the School and spearheaded campus-wide efforts in genomics, proteomics, and computational biology. His laboratory research centers on a novel cellular organelle called a "vault" which was discovered in his laboratory. Dr. Rome is presently organizing a Nanoscience Interdisciplinnary Research Team, a collaboration of disciplines including cell biologists, engineers, chemists, and structural biologists who will engineer vaults so that they may one day be used in drug delivery and as components of nano-electrical machines.
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Champion, C. I. Kickhoefer, V. A. Liu, G. Moniz, R. J. Freed, A. S. Bergmann, L. L. Vaccari, D. Raval-Fernandes, S. Chan, A. M. Rome, L. H. Kelly, K. A. , A vault nanoparticle vaccine induces protective mucosal immunity, PLoS ONE, 2009, 4 ( 4), e5409.
Kickhoefer, V. A. Han, M. Raval-Fernandes, S. Poderycki, M. J. Moniz, R. J. Vaccari, D. Silvestry, M. Stewart, P. L. Kelly, K. A. Rome, L. H. , Targeting vault nanoparticles to specific cell surface receptors, ACS Nano, 2009, 3 ( 1), 27-36.
Ng Benny C, Yu Marcella, Gopal Ajaykumar, Rome Leonard H, Monbouquette Harold G, Tolbert Sarah H, Encapsulation of semiconducting polymers in vault protein cages., Nano letters, 2008, 8 (10), 3503-9.
Xia Tian, Rome Leonard, Nel Andre, Nanobiology: particles slip cell security., Nature materials, 2008, 7 (7), 519-20.
Yu Marcella, Ng Benny C, Rome Leonard H, Tolbert Sarah H, Monbouquette Harold G, Reversible pH lability of cross-linked vault nanocapsules., Nano letters, 2008, 8 (10), 3510-5.
Esfandiary Sarah H, Kickhoefer Sarah H, Rome Sarah H, Joshi Sarah H, Middaugh Sarah H, Structural stability of vault particles., Journal of pharmaceutical sciences, 2008, 8 (10).
Anderson Daniel H, Kickhoefer Valerie A, Sievers Stuart A, Rome Leonard H, Eisenberg David, Draft crystal structure of the vault shell at 9-A resolution., PLoS biology, 2007, 5 (11), e318.
Kaddis Catherine S, Lomeli Shirley H, Yin Sheng, Berhane Beniam, Apostol Marcin I, Kickhoefer Valerie A, Rome Leonard H, Loo Joseph A, Sizing large proteins and protein complexes by electrospray ionization mass spectrometry and ion mobility., Journal of the American Society for Mass Spectrometry, 2007, 18 (7), 1206-16.
Goldsmith Lisa E, Yu Marcella, Rome Leonard H, Monbouquette Harold G, Vault nanocapsule dissociation into halves triggered at low pH., Biochemistry, 2007, 46 (10), 2865-75.
Slesina Marco, Inman Elisabeth M, Moore Ann E, Goldhaber Joshua I, Rome Leonard H, Volknandt Walter, Movement of vault particles visualized by GFP-tagged major vault protein., Cell and tissue research, 2006, 324 (3), 403-10.
Poderycki Michael J, Kickhoefer Valerie A, Kaddis Catherine S, Raval-Fernandes Sujna, Johansson Erik, Zink Jeffrey I, Loo Joseph A, Rome Leonard H, The vault exterior shell is a dynamic structure that allows incorporation of vault-associated proteins into its interior., Biochemistry, 2006, 45 (39), 12184-93.
Kickhoefer Valerie A, Garcia Yvette, Mikyas Yeshi, Johansson Erik, Zhou Jing C, Raval-Fernandes Sujna, Minoofar Payam, Zink Jeffrey I, Dunn Bruce, Stewart Phoebe L, Rome Leonard H, Engineering of vault nanocapsules with enzymatic and fluorescent properties., Proceedings of the National Academy of Sciences of the United States of America, 2005, 102 (12), 4348-52.
Raval-Fernandes Sujna, Kickhoefer Valerie A, Kitchen Christina, Rome Leonard H, Increased susceptibility of vault poly(ADP-ribose) polymerase-deficient mice to carcinogen-induced tumorigenesis., Cancer research, 2005, 65 (19), 8846-52.
Slesina Marco, Inman Elisabeth M, Rome Leonard H, Volknandt Walter, Nuclear localization of the major vault protein in U373 cells., Cell and tissue research, 2005, 321 (1), 97-104.
Poderycki Michael J, Rome Leonard H, Harrington Lea, Kickhoefer Valerie A, The p80 homology region of TEP1 is sufficient for its association with the telomerase and vault RNAs, and the vault particle., Nucleic acids research, 2005, 33 (3), 893-902.
Emre Nil, Raval-Fernandes Sujna, Kickhoefer Valerie A, Rome Leonard H, Analysis of MVP and VPARP promoters indicates a role for chromatin remodeling in the regulation of MVP., Biochimica et biophysica acta, 2004, 1678 (1), 33-46.
Mikyas Yeshi, Makabi Miriam, Raval-Fernandes Sujna, Harrington Lea, Kickhoefer Valerie A, Rome Leonard H, Stewart Phoebe L, Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP., Journal of molecular biology, 2004, 344 (1), 91-105.
Liu Yie, Snow Bryan E, Kickhoefer Valerie A, Erdmann Natalie, Zhou Wen, Wakeham Andrew, Gomez Marla, Rome Leonard H, Harrington Lea, Vault poly(ADP-ribose) polymerase is associated with mammalian telomerase and is dispensable for telomerase function and vault structure in vivo., Molecular and cellular biology, 2004, 24 (12), 5314-23.
Kickhoefer Valerie A, Emre Nil, Stephen Andrew G, Poderycki Michael J, Rome Leonard H, Identification of conserved vault RNA expression elements and a non-expressed mouse vault RNA gene., Gene, 2003, 309 (2), 65-70.
Hu Yi, Stephen Andrew G, Cao Jin, Tanzer Lee R, Slapak Christopher A, Harrison Steadman D, Devanarayan Viswanath, Dantzig Anne H, Starling James J, Rome Leonard H, Moore Robert E, A very early induction of major vault protein accompanied by increased drug resistance in U-937 cells., International journal of cancer. Journal international du cancer, 2002, 97 (2), 149-56.
Kickhoefer Valerie A, Poderycki Michael J, Chan Edward K L, Rome Leonard H, The La RNA-binding protein interacts with the vault RNA and is a vault-associated protein., The Journal of biological chemistry, 2002, 277 (43), 41282-6.
Stephen, A. G. Raval-Fernandes, S. Huynh, T. Torres, M. Kickhoefer, V. A. Rome, L. H. , Assembly of vault-like particles in insect cells expressing only the major vault protein, J Biol Chem, 2001, 276 ( 26), 23217-20.
Kickhoefer, V. A. Liu, Y. Kong, L. B. Snow, B. E. Stewart, P. L. Harrington, L. Rome, L. H. , The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle, J Cell Biol, 2001, 152 ( 1), 157-64.
Siva, A. C. Raval-Fernandes, S. Stephen, A. G. LaFemina, M. J. Scheper, R. J. Kickhoefer, V. A. Rome, L. H. , Up-regulation of vaults may be necessary but not sufficient for multidrug resistance, Int J Cancer, 2001, 92 ( 2), 195-202.
Marbois, B. N. Faull, K. F. Fluharty, A. L. Raval-Fernandes, S. Rome, L. H. , Analysis of sulfatide from rat cerebellum and multiple sclerosis white matter by negative ion electrospray mass spectrometry, Biochim Biophys Acta, 2000, 1484 ( 1), 59-70.
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