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BIOGRAPHICAL SKETCH - PSTP - University of Pittsburgh

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<strong>BIOGRAPHICAL</strong> <strong>SKETCH</strong><br />

NAME POSITION TITLE<br />

Michael R. Shurin<br />

Associate Pr<strong>of</strong>essor <strong>of</strong> Pathology and Immunology<br />

eRA COMMONS USER NAME<br />

SHURINMR<br />

EDUCATION/TRAINING (Begin with baccalaureate or other initial pr<strong>of</strong>essional education, such as nursing, and include postdoctoral training.)<br />

INSTITUTION AND LOCATION<br />

DEGREE<br />

(if applicable)<br />

YEAR(s) FIELD OF STUDY<br />

Moscow State Medical School, Moscow, Russia MD/MS 1984 Medicine, Biochemistry<br />

National Mental Health Research Center, Moscow Postdoctoral 1986 Clinical Biochemistry<br />

Institute for Pharmacology USSR Acad. Med. Sci. PhD 1991 Immunopharmacology<br />

A. Positions and Honors.<br />

1984 - 1986 Postdoctoral Fellow, Laboratory <strong>of</strong> Clinical Biochemistry, All Union Research Center for Mental<br />

Health, Academy <strong>of</strong> Medical Science, Moscow, Russia<br />

1986 - 1991 Research Associate, Laboratory <strong>of</strong> Clinical Immunology, National Mental Health Research<br />

Center, Academy <strong>of</strong> Medical Science, Moscow, Russia<br />

1991 - 1996 Assistant Pr<strong>of</strong>essor, Department <strong>of</strong> Pathology, Div. <strong>of</strong> Immunopathology, <strong>University</strong> <strong>of</strong><br />

<strong>Pittsburgh</strong> School <strong>of</strong> Medicine, <strong>Pittsburgh</strong>, PA<br />

1996 - 2000 Assistant Pr<strong>of</strong>essor, Department <strong>of</strong> Surgery, Div. <strong>of</strong> Surgical Oncology, <strong>University</strong> <strong>of</strong> <strong>Pittsburgh</strong><br />

Medical Center and <strong>University</strong> <strong>of</strong> <strong>Pittsburgh</strong> Cancer Institute, <strong>Pittsburgh</strong>, PA<br />

2000 - Pres Associate Pr<strong>of</strong>essor, Department <strong>of</strong> Pathology, Sec. <strong>of</strong> Laboratory Medicine, <strong>University</strong> <strong>of</strong><br />

<strong>Pittsburgh</strong> Medical Center, <strong>Pittsburgh</strong>, PA<br />

2000 - Pres Associate Director, Clinical Immunopathology, UPMC, <strong>Pittsburgh</strong>, PA<br />

2002 - Pres Associate Pr<strong>of</strong>essor, Department <strong>of</strong> Immunology, UPMC, <strong>Pittsburgh</strong>, PA<br />

•<br />

Honors, Awards and Other Pr<strong>of</strong>essional Activities:<br />

Member, NIH Site Visit, <strong>University</strong> <strong>of</strong> California San Diego, San Diego, CA (1999)<br />

• Grant review committee: NIH NIAID Special Emphasis Panel (SEP) for PO1, 2000, 2001<br />

• External Reviewer, VA Merit Review Boards, 2000, 2001, 2002<br />

• Reviewer, ACGT (Alliance for Cancer Gene Therapy), 2002, 2003, 2004<br />

• Ad Hoc reviewer, OBM-1 Study Section, 2001, 2002, 2003<br />

• Ad Hoc reviewer, TTT Study Section, 2004, 2006<br />

• Chair, ZRG1 ONC-U (1) Study Section, 2005<br />

• Chair, ZHD1 DRG-D (CV) Review group, NIH, 2005<br />

• Ad hoc reviewer, PCTA-1 and 2 study sections, CDMRP/DoD, 2006, 2007<br />

• Ad hoc reviewer, ZRG1 F07-L20 Immunology Fellowship & AREA Study Section, NIH, 2007 (x3), 2008<br />

B. Selected publications (from ~100 total, in chronological order). Do not include publications submitted or in preparation.<br />

• Shurin MR. Dendritic cell presenting tumor antigen. Cancer Immunology Immunother., 43:158-164, 1996.<br />

• Shurin MR, Pandharipande PP, Zorina TD, Haluszczak C, Subbotin VM, Hunter O, Brumfield A, Storkus WJ,<br />

Maraskovsky E, Lotze MT. FLT3-ligand induces the generation <strong>of</strong> functionally active dendritic cells in mice.<br />

Cellular Immunology, 179:174-184, 1997.<br />

• Esche C, Maliszewski C, Lotze MT, Shurin MR. FLT3 Ligand administration inhibits tumor growth in murine<br />

melanoma and lymphoma. Cancer Res., 58:380-383, 1998.<br />

• Peron J-M, Subbotin VM, Haluszczak C, Maliszewski C, Lotze MT, Shurin MR. FLT3-Ligand Administration<br />

Inhibits Liver Metastases: Role <strong>of</strong> NK Cells. J.Immunol., 161:6164-6170, 1998.<br />

• Esche C, Lokshin A, Shurin G, Rabinovich H, Gastman BR, Lotze MT, Shurin MR. Tumors’ other immune<br />

targets: Dendritic cells. J.Leukoc. Biol., 336-344,1999.<br />

• Esche C, Gambotto A, Satoh Y, Robbins PD, Watkins SC, Lotze MT, Shurin MR. CD40L inhibits tumorinduced<br />

apoptosis in dendritic cells and tumor growth. Eur. J. Immunol., 29:2148-2155, 1999.<br />

• Pirtskhalaishvili G, Shurin GV, Yurkovetsky ZR, Esche C, Gambotto A, Robbins P, Shurin MR. Transduction<br />

<strong>of</strong> dendritic cells with Bcl-xL increases their resistance to prostate cancer-induced apoptosis and antitumor<br />

effect in mice. J. Immunol. 165:1956-1964, 2000.<br />

• Pirtskhalaishvili G, Shurin GV, Esche C, Salup RR, Lotze MT, Shurin MR. Protection <strong>of</strong> human dendritic cells<br />

from prostate cancer-induced apoptosis by IL-12 and IL-15 is mediated by the Bcl-2 family <strong>of</strong> proteins. British<br />

J. Cancer, 83(4):506-513, 2000.<br />

• Esche C, Cai Q, Hunter O, Peron J-M, Maliszewski C, Wahl M, Lotze MT, Shurin MR. Interleukin-12 and Flt3<br />

ligand differentially promote dendropoiesis in vivo. Eur. J. Immunol., 30(9):2565-2575, 2000.


• Shurin GV, Shurin MR, Bykovskaia S, Shogan J, Lotze MT, Barksdale EM. Neuroblastoma-derived<br />

gangliosides inhibit dendritic cell generation and function. Cancer Res., 61:363-369, 2001.<br />

• Aalamian M, Pirtskhalaishvili G, Esche C, Shurin GV, Huland E, Huland H, Shurin MR. Human prostate<br />

cancer regulates generation and maturation <strong>of</strong> monocyte-derived dendritic cells. Prostate, 46: 68-75, 2001<br />

• Katsenelson NS, Shurin GV, Bykovskaia SN, Shogan J, Shurin MR. Human Small Cell Lung carcinoma and<br />

carcinoid tumor regulate dendritic cell maturation and function. Modern Pathology, 14(1): 40-45, 2001<br />

• Esche C, Shurin GV, Kirkwood JM, Wang GQ, Rabinowitz H, Pirtskhalaishvili G, Shurin MR. TNF-αpromoted<br />

expression <strong>of</strong> Bcl-2 and inhibition <strong>of</strong> mitochondrial cytochrome c release mediate resistance <strong>of</strong><br />

mature dendritic cells to melanoma-induced apoptosis. Clinical Cancer Res., 7:974s-979s, 2001<br />

• Pirtskhalaishvili G, Esche C, Shurin GV, Trump D, Shurin MR. TNF-α-mediated protection <strong>of</strong> dendritic cells<br />

from prostate cancer-induced cell death. Prost. Cancer Prost. Dis., 48: 667-669, 2001<br />

• Shurin MR, Yurkovetsky ZR, Tourkova IL, Balkir L, Shurin GV. Inhibition <strong>of</strong> CD40 expression and CD40mediated<br />

dendritic cell function by tumor-derived IL-10. Intl. J. Cancer. 101:61-68, 2002.<br />

• Satoh Y, Esche C, Gambotto A, Shurin GV, Yurkovetsky ZR, Robbins PD, Watkins SC, Todo S, Lotze MT,<br />

Herberman R, Shurin MR. Local Administration <strong>of</strong> IL-12-transfected Dendritic Cells Induces Antitumor<br />

Immune Responses to Colon Adenocarcinoma in the Liver in Mice. J. Exp. Therap.Oncol. 2:337-349, 2002.<br />

• Tourkova IL, Yurkovetsky ZR, Gambotto A, Makarenkova V, Perez L, Balkir L, Robbins PD, Shurin MR,<br />

Shurin GV. Increased Function and Survival <strong>of</strong> IL-15-transduced Human Dendritic Cells are Mediated by Upregulation<br />

<strong>of</strong> IL-15Rα and Bcl-2. J Leukoc Biol., 72:1037-1045, 2002.<br />

• Tourkova IL, Yamabe K, Chatta G, Shurin GV, Shurin MR. NK cells mediate Flt3 ligand-induced protection <strong>of</strong><br />

dendritic cell precursors in vivo from inhibition by prostate carcinoma in the bone marrow metastasis model.<br />

J. Immunotherapy, 26:468-472, 2003.<br />

• Aalamian M, Tourkova IL, Chatta G, Lilja H, Huland E, Huland H, Shurin GV, Shurin MR Inhibition <strong>of</strong><br />

Dendropoiesis by Tumor-derived and Purified PSA. J. Urology, 170:2026-2030, 2003.<br />

• Makarenkova VP, Shurin GV, Tourkova IL, Balkir L, Pirtskhalaishvili G, Gerein V, Siegfried JM, Shurin MR.<br />

Lung cancer-derived bombesin-like peptides down-regulate the generation and function <strong>of</strong> human dendritic<br />

cells. J. Neuroimmunology. 145:55-67, 2003.<br />

• Tourkova IL, Yamabe K, Foster B, Chatta G, Shurin GV, Shurin MR. Murine prostate cancer both in vitro and<br />

in vivo inhibits dendritic cell generation from bone marrow precursors. Prostate, 59:203-213, 2004.<br />

• Balkir L, Shurin GV, Robbins PD, Chatta G, Shurin MR. Comparative analysis <strong>of</strong> dendritic cells transduced<br />

with different anti-apoptotic molecules: Sensitivity to tumor-induced apoptosis. J Gene Med. 6:537-544, 2004.<br />

• Shurin GV, Chatta GS, Tourkova IL, Zorina TD, Esche C, Shurin M.R. Regulation <strong>of</strong> dendritic cell expansion<br />

in aged athymic nude mice by FLT3 ligand. Exper. Gerontol., 39:339-348, 2004.<br />

• Guruli G, Pflug BR, Pecher S, Makarenkova V, Shurin MR, Nelson JB. Function and survival dendritic cells<br />

depend on endothelin-1 and endothelin receptors autocrine loops. Blood, 104:2107-2115, 2004.<br />

• Whiteside TL, Stanson J, Shurin MR, Ferrone S. Antigen-Processing Machinery in Human Dendritic Cells:<br />

Up-Regulation by Maturation and Down-Regulation by Tumor Cells. J. Immunol. 173:1526–1534, 2004.<br />

• Perez L, Collins B, Shurin MR, Shurin GV. Comparative analysis <strong>of</strong> CD1a+, S100+, CD11c+, and CD83+<br />

human dendritic cells in normal, premalignant and tumor tissues. Histol. Histopath. 20: 1165-1172, 2005.<br />

• Shurin GV, Tourkova IL, Chatta GS, Schmidt G, Wei S, Djue J, Shurin MR. Small Rho GTPases Regulate<br />

Antigen Presentation in Dendritic Cells. J. Immunol. 174:3394-3400, 2005.<br />

• Shurin GV, Ferris R, Tourkova IL, Perez L, Lokshin A, Chatta GS, Shurin MR. Loss <strong>of</strong> new chemokine<br />

CXCL14 in tumor tissue is associated with low Infiltration by dendritic cells, while restoration <strong>of</strong> human<br />

CXCL14 expression in tumor cells causes attraction <strong>of</strong> dendritic cells both in vitro and in vivo. J. Immunol.<br />

174:5490-5498, 2005.<br />

• Tourkova IL, Shurin GV, Chatta GS, Perez L, Finke J, Whiteside TL, Ferrone S, Shurin MR. Restoration by<br />

IL-15 <strong>of</strong> MHC class I antigen processing machinery in human dendritic cells inhibited by tumor-derived<br />

gangliosides. J. Immunol. 175: 3045-3052, 2005.<br />

• Yurkovetsky ZR, Shurin GV, Barry DA, Schuh AC, Shurin MR, Robbins PD. Comparative Analysis <strong>of</strong><br />

Antitumor Activity <strong>of</strong> CD40L, RANKL, and 4-1BBL in vivo Following Intratumoral Administration <strong>of</strong> Viral<br />

Vectors or Transduced Dendritic Cells. J Gene Medicine, 8(2):129-37, 2006.<br />

• Shurin MR, Shurin GV, Lokshin A, Yurkovetsky ZR, Gutkin DW, Chatta GS, Zhong H, Han B, Ferris RL.<br />

Intratumoral cytokines/chemokines.growth factors and tumor infiltrating dendritic cells: Friends or enemies?<br />

Cancer Metastasis Reviews, 25(3): 333-356, 2006.<br />

• Tourkova IL, Shurin GV, Wei S, Shurin MR. Small Rho GTPases mediate tumor-induced inhibition <strong>of</strong><br />

endocytic activity <strong>of</strong> dendritic cells. J. Immunol. 178(12): 7787-7793, 2007.<br />

• Shurin M, Smolkin Y. Immune-mediated diseases: where do we stand? Adv.Exp.Med.Biol. 601:3-12, 2007.<br />

• Zhong H, Han B, Tourkova IL, Lokshin A, Rosenbloom A, Shurin MR, Shurin GV. Low-Dose Paclitaxel Prior<br />

to Intratumoral Dendritic Cell Vaccine Modulates Intratumoral Cytokine Network and Lung Cancer Growth.<br />

Clin. Cancer Res. 13(18): 5455-5462, 2007.<br />

• Shurin MR. Immune-mediated diseases: from theory to therapy. IDrugs 10(11): 762-764, 2007.


C. Research Support. List selected ongoing or completed (during the last three years) research projects (federal and<br />

non-federal support). Begin with the projects that are most relevant to the research proposed in this application. Briefly<br />

indicate the overall goals <strong>of</strong> the projects and responsibilities <strong>of</strong> principal investigator identified above.<br />

Shurin, Michael R.<br />

ONGOING<br />

2RO1 CA84270 Shurin (Principal Investigator) 02/01/04 – 01/30/09<br />

30%<br />

NIH/NCI<br />

Control <strong>of</strong> Dendritic Cell Generation and Function by Tumor<br />

The aims <strong>of</strong> this grant is to evaluate the regulation <strong>of</strong> dendritic cell<br />

maturation by tumor-derived factors and examine the role <strong>of</strong> small<br />

Rho GTPaeases in these mechanisms in the murine system.<br />

Shurin, Michael R.<br />

ONGOING<br />

P20 Herberman (Principal Investigator) 5P20CA103730<br />

NIH Shurin (Co-investigator)<br />

Cancer and Aging Center Planning Grant<br />

Shurin, Michael R.<br />

ONGOING<br />

DOD (Idea Award) PC050252 Shurin (Principal Investigator)<br />

Epigenetic regulation <strong>of</strong> chemokine expression in Prostate Cancer<br />

The major focus <strong>of</strong> this project is to determine the mechanisms<br />

responsible for down-regulating expression <strong>of</strong> chemokines in<br />

prostate cancer cell lines and primary tumors<br />

10/01/03 – 09/30/08<br />

12/01/05 - 11/30/08<br />

Shurin, Michael R.<br />

COMPLETED<br />

RO1 CA84270 Shurin (Principal Investigator)<br />

NIH/NCI<br />

Control <strong>of</strong> Dendritic Cell Generation and Function by Tumor<br />

The aims <strong>of</strong> this grant was to evaluate regulation <strong>of</strong> dendritic cell maturation by<br />

melanoma- and neuroblastoma-derived gangliosides and other factors and<br />

examine immunotherapeutic approaches to protect dendropoiesis<br />

Shurin, Michael R.<br />

COMPLETED<br />

RO1 CA80126 Shurin (Principal Investigator)<br />

NIH/NCI<br />

Tumor Associated Dendritic Cells<br />

The major goals were to determine the trafficking and behavior <strong>of</strong> dendritic cells in<br />

the tumor tissue and evaluate the role <strong>of</strong> FLT3 ligand in DC regulation.<br />

Shurin, Michael R.<br />

COMPLETED<br />

DAM017-00-1-0099 Shurin (Principal Investigator)<br />

DOD (Idea Award)<br />

Immune Gene Therapeutic Correction <strong>of</strong> Disordered Dendritic Cells in Prostate<br />

Cancer<br />

The major focus <strong>of</strong> this project was the development <strong>of</strong> new adenovirus vectors for<br />

targeting murine dendritic cells. In addition, the project focuses on evaluation <strong>of</strong><br />

means to generate DC in vitro and determine ways to express genes in these cells.<br />

Shurin, Michael R.<br />

COMPLETED<br />

5%<br />

30%<br />

12/01/99 – 1/30/03<br />

12/01/98 – 1/30/03<br />

02/01/00 - 03/31/03


PO-99013 Shurin (Principal Investigator)<br />

The <strong>Pittsburgh</strong> Foundation for Medical Research (Clinical Trial Support Program)<br />

New Approach for Prostate Cancer Therapy: Dendritic Cell Protected from Tumorinduced<br />

Death<br />

The aim <strong>of</strong> this project is to prepare a randomized phase I/II clinical trial to evaluate<br />

the efficacy <strong>of</strong> immunization <strong>of</strong> prostate cancer patients using autologous dendritic<br />

cells protected from apoptosis.<br />

Shurin, Michael R.<br />

COMPLETED<br />

UPCI Lung Cancer SPORE Project Shurin (Principal Investigator)<br />

Development Research Pilot Project Grant<br />

Molecular targets for reversal <strong>of</strong> lung cancer-mediated immunosuppression<br />

The aim <strong>of</strong> this study is to evaluate human lung cancer-derived factors responsible<br />

for alterations <strong>of</strong> dendritic cell ability to induce efficient antitumor immune<br />

responses.<br />

Shurin, Michael R.<br />

COMPLETED<br />

Prostate and Urologic Cancer Center Pilot Project Support<br />

Shurin (Principal Investigator)<br />

<strong>University</strong> <strong>of</strong> <strong>Pittsburgh</strong> Cancer Institute<br />

Effective Protection <strong>of</strong> Human Dendritic Cells from Prostate Cancer Induced Cell<br />

Death<br />

The major goals <strong>of</strong> this pilot project was to collect preliminary data evaluating in<br />

vitro effects <strong>of</strong> human cytokines on the survival <strong>of</strong> cultured dendritic cells and<br />

determine the optimal conditions for cytokine-induced protection <strong>of</strong> dendritic cells<br />

from prostate cancer-induced apoptosis.<br />

Shurin, Michael R.<br />

COMPLETED<br />

Competitive Medical Research Fund Shurin (Principal Investigator)<br />

<strong>University</strong> <strong>of</strong> <strong>Pittsburgh</strong> Medical Center<br />

Induction <strong>of</strong> an Antitumor Response Using Dendritic Cells: Murine Models <strong>of</strong><br />

Combination Therapy with IL-12<br />

This study focused on the combination <strong>of</strong> dendritic cells and IL-12 immunotherapy<br />

in murine tumor systems and mechanisms regulating migration <strong>of</strong> dendritic cells to<br />

the site <strong>of</strong> the tumor.<br />

Shurin, Michael R.<br />

COMPLETED<br />

George Heckman Award Shurin (Principal Investigator)<br />

American Cancer Society and UPCI<br />

FLT3 Ligand as a Novel Cytokine for Anticancer Immunotherapy<br />

The objective <strong>of</strong> this project was to determine the antitumor efficacy <strong>of</strong> a new<br />

dendritic cell growth factor FLT3 ligand using murine tumor models.<br />

07/01/99 –<br />

06/30/02<br />

02/01/02–<br />

12/31/03<br />

01/01/99 –<br />

12/31/99<br />

07/01/97 –<br />

06/30/98<br />

10/01/96 –<br />

09/30/97

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