- ASSISTANT PROFESSOR Oncological Sciences
Research Scholar Award
American Cancer Society
US Department of Defense
Translational Research Award
Susan G. Komen Breast Cancer Foundation
US Department of Defense
US Department of Defense
Career Development Award, Derald H. Ruttenberg Treatment Center
Mount Sinai School of Medicine
Microtubules are dynamic protein polymers that are essential for a myriad of cellular functions, including mitosis, intracellular transport, polarity, and motility. During cell division, the mitotic spindle, which is composed of microtubule polymers of alpha/beta tubulin heterodimers, plays the primary role in the segregation of chromosomes to the two daughter cells. The movement of chromosomes toward the spindle poles is made possible by the dynamic instability of microtubules that switches between phases of elongation and shortening. The dynamics of microtubule during the different phases of the cell cycle is regulated by two major classes of proteins, microtubule-stabilizing proteins and microtubule destabilizing proteins. Stathmin is the founding member of a family of microtubule-destabilizing proteins that regulate the polymerization and depolymerization of microtubules. It plays a critically important role in the assembly and disassembly of the mitotic spindle. Thus, stathmin is one of the key regulators of the microtubule cytoskeleton and the mitotic spindle. In addition to its well-documented role in cell proliferation, stathmin also plays an important role in cell motility and cancer metastasis. Interestingly, stathmin is expressed at high levels in nearly all types of human cancers and its overexpression is directly linked to disease progression. Hence, stathmin provides an attractive molecule to target in cancer therapies that aim to disrupt the mitotic apparatus of proliferating cancer cells.
A major focus of my research program is geared towards developing novel cancer therapies by using stathmin as a potential therapeutic target, mainly in solid tumor malignancies including breast and prostate cancer. We are developing two different approaches for targeting stathmin function in cancer cells. As a first step, we designed ribozymes that target stathmin mRNA for degradation in cancer cells. We had previously cloned the genes that encode these ribozymes in adenoviral gene transfer vectors. We are currently testing the utility of these recombinant adenoviruses in in vitro and in vivo models of breast cancer. These studies may lead to the development of stathmin based gene therapy strategies for the treatment of localized early stage breast cancer. A second strategy is aimed towards developing systemic pharmacological approaches that target stathmin function by interfering with its interaction with tubulin in widespread tumor cells. Towards this end, we are testing stathmin-like peptide drugs in in vitro and in vivo models of breast cancer. We are also developing an assay to screen chemical libraries in a high throughput setting to identify small molecule inhibitors that interfere with stathmin-tubulin interaction. The future development of such candidates into effective drugs may offer hope to a large number of patients who die from this dreadful malignancy.
Miceli C, Tejada A, Castaneda A, Mistry SJ. Cell cycle inhibition therapy that targets stathmin in in vitro and in vivo models of breast cancer. Cancer gene therapy 2013 May; 20(5).
Mistry SJ, Oh WK. New paradigms in microtubule-mediated endocrine signaling in prostate cancer. Molecular cancer therapeutics 2013 May; 12(5).
Scher BM, Mistry SJ, Haque NS, Scher W. Isolation and characterization of a large soluble form of fibronectin that stimulates adhesion, spreading, and alignment of mouse erythroleukemia cells. Experimental cell research 2010 Sep; 316(15).
Mistry SJ, Atweh GF. Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer. Molecular cancer therapeutics 2006 Dec; 5(12).
Mistry SJ, Bank A, Atweh GF. Synergistic antiangiogenic effects of stathmin inhibition and taxol exposure. Molecular cancer research : MCR 2007 Aug; 5(8).
Mistry SJ, Atweh GF. Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. The Mount Sinai journal of medicine, New York 2002 Oct; 69(5).
Mistry SJ, Bank A, Atweh GF. Targeting stathmin in prostate cancer. Molecular cancer therapeutics 2005 Dec; 4(12).
Mistry SJ, Atweh GF. Stathmin inhibition enhances okadaic acid-induced mitotic arrest: a potential role for stathmin in mitotic exit. The Journal of biological chemistry 2001 Aug; 276(33).
Mistry SJ, Benham CJ, Atweh GF. Development of ribozymes that target stathmin, a major regulator of the mitotic spindle. Antisense & nucleic acid drug development 2001 Feb; 11(1).
Mistry SJ, Li HC, Atweh GF. Role for protein phosphatases in the cell-cycle-regulated phosphorylation of stathmin. The Biochemical journal 1998 Aug; 334 ( Pt 1).
Mistry SJ, Atweh GF. Stathmin expression in immortalized and oncogene transformed cells. Anticancer research; 19(1A).
Iancu C, Mistry SJ, Arkin S, Atweh GF. Taxol and anti-stathmin therapy: a synergistic combination that targets the mitotic spindle. Cancer research 2000 Jul; 60(13).
Iancu C, Mistry SJ, Arkin S, Wallenstein S, Atweh GF. Effects of stathmin inhibition on the mitotic spindle. Journal of cell science 2001 Mar; 114(Pt 5).
Luo XN, Arcasoy MO, Brickner HE, Mistry S, Schechter AD, Atweh GF. Regulated expression of p18, a major phosphoprotein of leukemic cells. The Journal of biological chemistry 1991 Nov; 266(31).
Mistry S, Luo XN, Atweh GF. Transcriptional regulation of phosphoprotein p18 during monocytic differentiation of U937 leukemic cells. Cellular & molecular biology research 1995; 41(2).
Luo XN, Mookerjee B, Ferrari A, Mistry S, Atweh GF. Regulation of phosphoprotein p18 in leukemic cells. Cell cycle regulated phosphorylation by p34cdc2 kinase. The Journal of biological chemistry 1994 Apr; 269(14).
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Dr. Mistry has not yet completed reporting of Industry relationships.
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
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