Leonard H. Rome

Last updated

Leonard H. Rome is a cell biologist and biochemist who has been a faculty member of the David Geffen School of Medicine at UCLA, since he joined the Department of Biological Chemistry there, in 1979. He became a full professor in 1988 and has also served as the Senior Associate Dean for Research in the Geffen School of Medicine from 1997 to 2012. He is the Associate Director of the California NanoSystems Institute (CNSI) since 2004, and was Interim Director from 2007-2009. In addition, he served from 2001 to 2005 as University of California, Los Angeles (UCLA) Associate Vice Chancellor for Research for the Life and Health Sciences.

Contents

Rome earned his B.S. in chemistry and M.S. and Ph.D. in biochemistry (biological chemistry) at the University of Michigan Health System with William E.M. Lands. He was a postdoctoral fellow at the National Institutes of Health, where he worked with Elizabeth F. Neufeld on lysosome biogenesis and lysosomal storage diseases. His laboratory research at UCLA centers on a novel cellular organelle called a vault which he and a former postdoc, Nancy Kedersha, discovered in 1986. [1] Rome is the past chair of the Association of American Medical Colleges (AAMC) Group on Research Advancement and Development (GRAND).

Research

Rome’s lab is using molecular engineering of a naturally occurring cellular structure called a vault to develop a flexible, targetable nanoscale capsule. Vaults are abundant cellular particles of unknown function found in nearly all eukaryotes (cells containing a nucleus). In 1986, Rome and his then postdoctoral associate Nancy Kedersha were the first investigators to isolate and describe the vault particle. [1] Cryo-electron microscopy, plus 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 high potential to encapsulate, protect, and deliver compounds. Using a well-characterized insect virus into which a cloned gene can be easily inserted, it is possible to produce large amounts of a given protein in cultured insect cells.

The Rome lab has collaborated with several groups to use the baculovirus system to produce large amounts of vaults. When the major vault protein (MVP) is expressed in insect cells, vault particles are assembled on polysomes (polyribosomes) in the cytoplasm. [2] By using molecular genetic methods to modify the gene encoding the major vault protein, vault particles 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.

In 2003, Rome cofounded a company called Vault Pharma Inc., [3] to move the first vault therapeutic into a phase I clinical trial. This vault is packaged with a chemokine and will be used to activate the immune system to attack lung cancer. [4] [5] As of 2012, Vault Pharma is working with Protein Sciences Corp., to develop the GLP/cGMP manufacture of this vault-based therapeutic.

Related Research Articles

Chemokine

Chemokines are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines.

CCL2

For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.

Macrophage inflammatory protein

Macrophage Inflammatory Proteins (MIP) belong to the family of chemotactic cytokines known as chemokines. In humans, there are two major forms, MIP-1α and MIP-1β that are now officially named CCL3 and CCL4, respectively. But we can sometimes encounter other names, especially in older literature, as LD78α, AT 464.1 and GOS19-1 for human CCL3 and AT 744, Act-2, LAG-1, HC21 and G-26 for human CCL4. Other macrophage inflammatory proteins include MIP-2, MIP-3 and MIP-5.

Chemokine ligand 28 (CCL28), also known as mucosae-associated epithelial chemokine (MEC), CCK1 and SCYA28, is a chemokine. CCL28 regulates the chemotaxis of cells that express the chemokine receptors CCR3 and CCR10. CCL28 is expressed by columnar epithelial cells in the gut, lung, breast and the salivary glands and drives the mucosal homing of T and B lymphocytes that express CCR10, and the migration of eosinophils expressing CCR3. This chemokine is constitutively expressed in the colon, but its levels can be increased by pro-inflammatory cytokines and certain bacterial products implying a role in effector cell recruitment to sites of epithelial injury. CCL28 has also been implicated in the migration of IgA-expressing cells to the mammary gland, salivary gland, intestine and other mucosal tissues. It has also been shown as a potential antimicrobial agent effective against certain pathogens, such as Gram negative and Gram positive bacteria and the fungus Candida albicans.

Chemokine ligands 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.

CCL7

Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.

CCL8

Chemokine ligand 8 (CCL8), also known as monocyte chemoattractant protein 2 (MCP2), is a protein that in humans is encoded by the CCL8 gene.

CCL11

C-C motif chemokine 11 also known as eosinophil chemotactic protein and eotaxin-1 is a protein that in humans is encoded by the CCL11 gene. This gene is encoded on three exons and is located on chromosome 17.

CCL20

Chemokine ligand 20 (CCL20) or liver activation regulated chemokine (LARC) or Macrophage Inflammatory Protein-3 (MIP3A) is a small cytokine belonging to the CC chemokine family. It is strongly chemotactic for lymphocytes and weakly attracts neutrophils. CCL20 is implicated in the formation and function of mucosal lymphoid tissues via chemoattraction of lymphocytes and dendritic cells towards the epithelial cells surrounding these tissues. CCL20 elicits its effects on its target cells by binding and activating the chemokine receptor CCR6.

CCL18

Chemokine ligand 18 (CCL18) is a small cytokine belonging to the CC chemokine family. The functions of CCL18 have been well studied in laboratory settings, however the physiological effects of the molecule in living organisms have been difficult to characterize because there is no similar protein in rodents that can be studied. The receptor for CCL18 has been identified in humans only recently, which will help scientists understand the molecule's role in the body.

CCL21

Chemokine ligand 21 (CCL21) is a small cytokine belonging to the CC chemokine family. This chemokine is also known as 6Ckine, exodus-2, and secondary lymphoid-tissue chemokine (SLC). The gene for CCL21 is located on human chromosome 9. CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7.

CCL17

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to allergic diseases.

CC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins since they span the cell membrane seven times. To date, ten true members of the CC chemokine receptor subfamily have been described. These are named CCR1 to CCR10 according to the IUIS/WHO Subcommittee on Chemokine Nomenclature.

Vault RNA

Many eukaryotic cells contain large ribonucleoprotein particles in the cytoplasm known as vaults. The vault complex comprises the major vault protein (MVP), two minor vault proteins, and a variety of small untranslated RNA molecules. Given the association with the nuclear membrane and the location within the cell, vaults are thought to play roles in intracellular and nucleocytoplasmic transport processes. Also, given that the structure and protein composition are highly conserved among species, it is believed that the roles vault plays are integral to eukaryotic function.

C-C chemokine receptor type 7

C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21).

C-C chemokine receptor type 6

Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196. The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids.

Major vault protein

Major vault protein is a protein that in humans is encoded by the MVP gene. 78 copies of the protein assemble into the large compartments called vaults, illustrated and discussed in the article on Vault (organelle).

CCL3L1

Chemokine ligand 3-like 1, also known as CCL3L1, is a protein which in humans is encoded by the CCL3L1 gene.

PARP4

Poly [ADP-ribose] polymerase 4 is an enzyme that in humans is encoded by the PARP4 gene.

Vault (organelle) Eukaryotic organelle

The vault or vault cytoplasmic ribonucleoprotein is a eukaryotic organelle whose function is not yet fully understood. Discovered and isolated by Nancy Kedersha and Leonard Rome in 1986, vaults are cytoplasmic organelles which, when negative-stained and viewed under an electron microscope, resemble the arches of a cathedral's vaulted ceiling, with 39-fold symmetry. They are present in many types of eukaryotic cells, and appear to be highly conserved among eukaryotes.

References

  1. 1 2 Kedersha, N. L.; Rome, L. H. (1986-09-01). "Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA". The Journal of Cell Biology. 103 (3): 699–709. doi:10.1083/jcb.103.3.699. ISSN   0021-9525. PMC   2114306 . PMID   2943744.
  2. ↑ Mrazek, Jan; Toso, Daniel; Ryazantsev, Sergey; Zhang, Xing; Zhou, Z. Hong; Fernandez, Beatriz Campo; Kickhoefer, Valerie A.; Rome, Leonard H. (2014-11-25). "Polyribosomes are molecular 3D nanoprinters that orchestrate the assembly of vault particles". ACS Nano. 8 (11): 11552–11559. doi:10.1021/nn504778h. ISSN   1936-086X. PMC   4245718 . PMID   25354757.
  3. ↑ Vault Pharma Inc.
  4. ↑ Sharma, Sherven; Zhu, Li; Srivastava, Minu K.; Harris-White, Marni; Huang, Min; Lee, Jay M.; Rosen, Fran; Lee, Gina; Wang, Gerald (2013-01-01). "CCL21 Chemokine Therapy for Lung Cancer". International Trends in Immunity. 1 (1): 10–15. ISSN   2326-3121. PMC   4175527 . PMID   25264541.
  5. ↑ Kar, Upendra K.; Srivastava, Minu K.; Andersson, Asa; Baratelli, Felicita; Huang, Min; Kickhoefer, Valerie A.; Dubinett, Steven M.; Rome, Leonard H.; Sharma, Sherven (2011-01-01). "Novel CCL21-vault nanocapsule intratumoral delivery inhibits lung cancer growth". PLOS ONE. 6 (5): e18758. Bibcode:2011PLoSO...618758K. doi: 10.1371/journal.pone.0018758 . ISSN   1932-6203. PMC   3086906 . PMID   21559281.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.