Faculty & Staff at TUC

Michael  Ellerby

Michael Ellerby

College: COP

Department: Biological & Pharmaceutical Sciences

Title: Professor and Chair, Biological & Pharmaceutical Sciences

Phone: (707) 638-5907

Fax: (707) 638-5959

E-Mail: michael.ellerby@tu.edu

Office: Administration & Faculty 2, Rm. 208

Institution Degree Field of Study Obtained
University of California, Santa Cruz B.S. Chemistry 1979
University of California, Santa Cruz Ph.D. Chemical Physics 1986

PHRM 602: Pharmaceutical Sciences (Participating Faculty member)
PHRM 606 Pharmaceutical Sciences (Participating Faculty member)
PHRM 610: Pharmaceutical Sciences (Participating Faculty member)
PHRM 614 Pharmaceutical Sciences (Participating Faculty member)

Drug Design for Cancer and Arthritis

My laboratory has worked since 1999 on targeted cell deletion technologies (TCDT) to treat cancer and age-associated degenerative joint disease, and has designed a new class of drugs to fight autoimmune diseases (or those with a significant autoimmune component) such as osteo- and rheumatoid arthritis. This class of drugs may also have application for HIV/AIDS, a disease that new evidence suggests may result from an autoimmune reaction triggered by the virus.

 

Targeted Endothelial Cell Deletion for Cancer, Arthritis, and Obesity

We have developed a strategy to treat cancer by targeting and killing the endothelial cells that form the blood vessels of a tumor, which then destroys those blood vessels, and starves the tumor to death. Our work was featured on the cover of the November 1999 issue of Nature Medicine. At the heart of our approach is the design and synthesis of novel dual-purpose hunter-killer peptides (HKPs) that are composed of two parts. The first part is a hunter peptide that guides the HKP to tumor blood vessels. The second is a killer peptide designed to be nontoxic to normal blood vessels but deadly to tumor blood vessels. HKPs have strong anti-tumor activity in models of breast and prostate cancer—reducing tumor volume and metastasis, and prolonging survival.

Beyond cancer therapy, HKPs have also shown broad application in (1) arthritis: HKPs targeted to the synovial vasculature have strong anti-inflammatory effects in a mouse model of arthritis (collagen-induced); (2) obesity: HKPs targeted to the normal blood vessels that feed fat deposits decrease obesity in a transgenic mouse model of obesity; and (3) organ reduction: HKPs targeted to normal prostate vasculature reduce the size of the prostate gland, and have a strong anticancer effect in the transgenic mouse model of prostate carcinoma (TRAMP). Thus HKPs have been developed to treat the three most costly age-associated diseases in the United States—heart disease (obesity) (~$300 billion), cancer (~$200 billion), and degenerative joint disease (~$200 billion).

Recent work from our laboratory includes the discovery that HKP dimers, and a combination therapy of this dimer and a nanoparticle formulation of the anticancer drug taxol developed by American Bioscience Inc. are also very effective anticancer therapies. As a complement to our antiangiogenic HKP therapy, we have developed a small globular protein (SGP) as an antineoplastic agent that directly kills tumor cells, through a mechanism of cell plasma membrane disruption that leaves surrounding extracellular matrix (ECM) unaffected. SGP was featured on the cover of the September 2003 issue of the Journal of Biological Chemistry, where we show that it has a strong antitumor activity in models of breast, lung, gastric, and prostate cancer—reducing tumor volume and metastasis, and prolonging survival.

Targeted B-cell deletion for arthritis and autoimmune disease

In collaboration with the Institute for Applied Biomedicine our lab has developed a new class of drugs that selectively kills only the B-cells making antibodies to a specific disease-causing antigen, leaving all other B-cells (and also the rest of the immune system) unharmed. This is a powerful technique since there are many so-called autoimmune diseases directly caused by a very tiny subpopulation of B-cells (usually < 10-3 of total B-cell population). These B-cells make antibodies that are the lynchpins of the disease process. Thus, eliminating them stops the disease process. B-cells must internalize (bring inside themselves) an antigen in order to make antibodies to that antigen. Our lab has developed a new class of drugs that selectively kills only the B-cells making antibodies to a specific disease-causing antigen, leaving all other B-cells (and also the rest of the immune system) unharmed. The antigen can be of foreign origin or native (autoimmune) origin. The drug has two parts—the antigen, or modified antigen, and a toxin (diphtheria A chain) that is harmless to the outside of a cell but deadly inside a cell (only one molecule required for death).

The mechanism of targeted B-cell killing is simple. Any B-cells attempting to make antibodies to the autoimmune disease-causing antigen are tricked into internalizing our drug, since it contains the antigen, and are then killed. Without B-cells making antibodies to the autoimmune disease-causing antigen, the autoimmune process cannot occur. B-cells not making antibodies to this antigen are left healthy to make the other antibodies we need in order to stay disease-free. The list of potential diseases that our therapy should apply to is well over 100 in number, and includes Graves’ disease, Addison’s disease, type I diabetes, Crohn’s disease, multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, as well as many B-cell mediated drug hypersensitivity reactions, allergies, and antibody reactions to therapeutic interventions such as xenotransplant rejection and serum-sickness reactions to antibodies from nonhuman sources.

National Institutes of Health/National Cancer Institute Grant (NIH RO1 CA 84262), “Novel Hunter Killer Peptides for Cancer Therapy.” $360,000/year to cover both direct and indirect costs. H. Michael Ellerby, Principal Investigator. 2000-2004

Department of Defense Prostate Cancer Grant (DAMD 17-01-01-0029), “Compre-hensive Development Program of Hunter-Killer Peptides for Prostate Cancer.” $250,000/year to cover both direct and indirect costs. H. Michael Ellerby, Principal Investigator. 2000-2004

ABI (American Bioscience Incorporated) Sponsored Research Grant, “Cancer and Aging.” $437,000/year to cover both direct and indirect costs. H. Michael Ellerby, Principal Investigator. 2000-2004

Joseph Drown Foundation, “Cancer and Aging.” $100,000/year to cover both direct and indirect costs. H. Michael Ellerby, Principal Investigator. 2004-2006

Institute of Applied Biomedicine, "A Novel B-Cell Deletion Technology for Autoimmune Disease," $50,000. H. Michael Ellerby, Principal Insvestigator. 2007-2009

1. Andrews FC, Ellerby HM. A Simple Equilibrium Statistical Mechanical Theory of Dense Hard Sphere Fluid Mixtures. J. Chem. Phys. 75:3542-3552, 1981
2. Andrews FC, Ellerby HM. A Simple Equilibrium Statistical Mechanical Theory of Dense Hard Sphere Fluid Mixtures, II. J. Chem. Phys. 77:2703-2704, 1982
3. Ellerby HM, Weakliem CL, Reiss H. Toward a Molecular Theory of Vapor-Phase Nucleation I. Identification of the Average Embryo. J. Chem. Phys. 95:9209-9218, 1991
4. Ellerby HM, Reiss H. Toward A Molecular Theory of Vapor-Phase Nucleation II. Fundamental Treatment of the Cluster Distribution. J. Chem. Phys. 97:5766-5772, 1992
5. Reiss H, Ellerby HM, Manzanares JA. Configurational Entropy of Microemulsions: The Fundamental Length Scale. J. Chem. Phys. 99:9930-9937, 1993
6. Ellerby HM. Distribution of density fluctuations in a molecular theory of vapor- phase nucleation. Physical Review. E. Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics 49:4287-4297., 1994
7. Ellerby LM, Ellerby HM, Park SM, Holleran AL, Murphy AN, Fiskum G, Kane DJ, Testa MP, Kayalar C, Bredesen DE. Shift of the cellular oxidation-reduction potential in neural cells expressing Bcl-2. J Neurochem 67:1259-67., 1996
9. Reiss H, Ellerby HM, Manzanares JA. Orstein-Zernike Equations in Statistical Geometry - Stable and Metastable States. J. Phys. Chem 100:5970-5981, 1996
10. Ellerby HM, Martin SJ, Ellerby LM, Naiem SS, Rabizadeh S, Salvesen GS, Casiano CA, Cashman NR, Green DR, Bredesen DE. Establishment of a cell-free system of neuronal apoptosis: comparison of premitochondrial, mitochondrial, and postmitochondrial phases. J Neurosci 17:6165-78., 1997
11. Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, Zhou Q, Ellerby HM, Ellerby LM, Bredesen D, Green DR, Reed JC, Froelich CJ, Salvesen GS. Pro-caspase-3 is a major physiologic target of caspase-8. J Biol Chem 273:27084-90., 1998
12. Ellerby HM, Arap W, Ellerby LM, Kain R, Andrusiak R, Rio GD, Krajewski S, Lombardo CR, Rao R, Ruoslahti E, Bredesen DE, Pasqualini R. Anti-cancer activity of targeted pro-apoptotic peptides. Nat Med 5:1032-8., 1999
13. Ellerby LM, Hackam AS, Propp SS, Ellerby HM, Rabizadeh S, Cashman NR, Trifiro MA, Pinsky L, Wellington CL, Salvesen GS, Hayden MR, Bredesen DE. Kennedy's disease: caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J Neurochem 72:185-95., 1999
14. Lee S, Ellerby HM, Sugihara G. De Novo Design and Synthesis of a Small Globular Protein Forming a Pore into Lipid Bilayers. In: ACS Protein Meeting, pp 15-22, 1999
15. Kluck RM, Ellerby LM, Ellerby HM, Naiem S, Yaffe MP, Margoliash E, Bredesen D, Mauk AG, Sherman F, Newmeyer DD. Determinants of cytochrome c pro-apoptotic activity. The role of lysine 72 trimethylation. J Biol Chem 275:16127-33., 2000
16. Lee S, Ellerby HM, Kiyota T, Sugihara G: DeNovo Design and Synthesis of Small Globular Protein Forming a Pore in Lipid Bilayers. In: Controlled Drug Delivery: Designing Technologies for the Future, pp 139-148. Ed by K Park and RJ Mrsny. Washington, DC, American Chemical Society, 2000
17. Matsumoto E, Kiyota T, Lee S, Sugihara G, Yamashita S, Meno H, Aso Y, Sakamoto H, Ellerby HM. Study on the packing geometry, stoichiometry, and membrane interaction of three analogs related to a pore-forming small globular protein. Biopolymers 56:96-108, 2000
18. Rabizadeh S, Ye X, Sperandio S, Wang JJ, Ellerby HM, Ellerby LM, Giza C, Andrusiak RL, Frankowski H, Yaron Y, Moayeri NN, Rovelli G, Evans CJ, Butcher LL, Nolan GP, Assa-Munt N, Bredesen DE. Neurotrophin dependence domain: a domain required for the mediation of apoptosis by the p75 neurotrophin receptor. J Mol Neurosci 15:215-29., 2000
19. del Rio G, Castro-Obregon S, Rao R, Ellerby HM, Bredesen DE. APAP, a sequence-pattern recognition approach identifies substance P as a potential apoptotic peptide. FEBS Lett 494:213-9., 2001
20. Gerlag DM, Borges E, Tak PP, Ellerby HM, Bredesen DE, Pasqualini R, Ruoslahti E, Firestein GS. Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature. Arthritis Res 3:357-61, 2001
21. Lee S, Furuya T, Kiyota T, Takami N, Murata K, Niidome Y, Bredesen DE, Ellerby HM, Sugihara G. De novo-designed peptide transforms Golgi-specific lipids into Golgi- like nanotubules. J Biol Chem 276:41224-8., 2001
22. Rao RV, Hermel E, Castro-Obregon S, del Rio G, Ellerby LM, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Mechanism of caspase activation. J Biol Chem 276:33869-74., 2001
23. Arap W, Haedicke W, Bernasconi M, Kain R, Rajotte D, Krajewski S, Ellerby HM, Bredesen DE, Pasqualini R, Ruoslahti E. Targeting the prostate for destruction through a vascular address. Proc Natl Acad Sci U S A 99:1527-31., 2002
24. Rao RV, Peel A, Logvinova A, del Rio G, Hermel E, Yokota T, Goldsmith PC, Ellerby LM, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett 514:122-8., 2002
25. Rao RV, Castro-Obregon S, Frankowski H, Schuler M, Stoka V, Del Rio G, Bredesen DE, Ellerby HM. Coupling Endoplasmic Reticulum Stress to the Cell Death Program. An Apaf-1-Independent Intrinsic Pathway. J Biol Chem 277:21836-42., 2002
26. Ellerby HM, Lee S, Ellerby LM, Chen S, Kiyota T, del Rio G, Sugihara G, Sun Y, Bredesen DE, Arap W, Pasqualini R. An artificially designed pore-forming protein with anti-tumor effects. J Biol Chem 278:35311-6, 2003
27. Furuya T, Kiyota T, Lee S, Inoue T, Sugihara G, Logvinova A, Goldsmith P, Ellerby HM. Nanotubules formed by highly hydrophobic amphiphilic alpha-helical peptides and natural phospholipids. Biophys J 84:1950-9, 2003
28. Rao RV, Poksay KS, Castro-Obregon S, Schilling B, Row RH, del Rio G, Gibson BW, Ellerby HM, Bredesen DE. Molecular components of a cell death pathway activated by endoplasmic reticulum stress. J Biol Chem 279:177-87, 2004
29. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11:372-80, 2004
30. Hermel E, Gafni J, Propp SS, Leavitt BR, Wellington CL, Young JE, Hackam AS, Logvinova AV, Peel AL, Chen SF, Hook V, Singaraja R, Krajewski S, Goldsmith PC, Ellerby HM, Hayden MR, Bredesen DE, Ellerby LM. Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Cell Death Differ 11:424-38, 2004
31. Sandoval CM, Geierstanger BH, Fujimura S, Balatbat C, Williams T, Unamuno J, Whiles-Lillig JA, Ellerby LM, Ellerby HM, Jennings P, and Plesniak LA. Structural Evaluation of a Novel Pro-apoptotic Peptide Coupled to CNGRC Tumor-Homing Sequence by NMR. Chem Biol Drug Design, 67: 417-424, 2006
32. Ellerby HM, Bredesen DE, Fujimura, and John V. Hunter-killer peptide (HKP) for targeted therapy. J. Med. Chem. 51: 5887-5892, 2008
33. Frankowski H, Alavez S, Mark K, Nelson J, Spilman P, Mollahan P, Rao R, Chen S, Lithgow G and Ellerby HM. Small amphipathic molecules extend the lifespan of Caenorhabditis elegans through a mechanism that involves a decrease in protein aggregation. Mechanisms of Ageing and Development 134: 69–78, 2013

1979 Chancellor’s Award, Outstanding Scientific Research
1979 University of California, Santa Cruz, Highest Honors on Thesis
1979 University of California, Santa Cruz, Highest Honors in Chemistry
1979 University of California Regents’ Fellowship
1980 University of California Regents’ Fellowship
1981 University of California Regents’ Fellowship
1982 University of California Regents’ Fellowship
1983 University of California Regents’ Fellowship
1985 University of California Outstanding Teaching Award
1994 Invited Leading Paper, Physical Review E
1995 Joseph Drown Fellowship, The Burnham Institute
1996 Joseph Drown Fellowship, The Burnham Institute
1996 Individual National Research Service Award — Senior Award
1997 Individual National Research Service Award — Senior Award
1998 Individual National Research Service Award — Senior Award
1999 Individual National Research Service Award — Senior Award
2007 Professor of the Year, Touro University College of Pharmacy
2007 Best Lecturer, Touro University College of Pharmacy                                              2012 Professor of the Year, Basic Science, Touro University College of Pharmacy

Employer Title From - To
University of California, Santa Cruz Instructor (Chemistry) 1977-1986
University of California, Santa Cruz Research Scholar in Chemical Physics/Instructor (Postdoctoral Position) 1986-1991
University of California, Los Angeles Senior Research Scholar in Chemical Physics (Postdoctoral Position) 1991-1994
The Burnham Institute for Medical Research Senior Research Scholar in Neurobiology (Postdoctoral Position) 1994-1995
The Burnham Institute for Medical Research Joseph Drown Research Fellow (Postdoctoral Position) 1995-1997
The Burnham Institute for Medical Research NIH Senior Fellow (Postdoctoral Position) 1997-1999
The Buck Institute for Age Research Assistant Professor 1999-2006
Touro University COP Associate Professor 2005-2007
Touro University COP Associate Professor and Chair, Department of Pharmaceutical Sciences 2007-present
Touro University COP Professor and Chair, Department of Biological and Pharmaceutical Sciences
Last Updated: 5/5/17