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M. Raza Zaidi, PhD

 

M. Raza Zaidi, PhD

 

Assistant Professor, Fels Institute for Cancer Research and Molecular Biology

Assistant Professor, Biochemistry

Telephone:  215-707-3821

Email: zaidi@temple.edu

 

Department of Biochemistry

Fels Institute for Cancer Research and Molecular Biology

 

Educational Background:

 

BA, Biological Sciences, Rutgers University, New Brunswick, NJ, 1994

 

PhD, Biochemistry and Molecular Biology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ, 1997-2003

 

Postdoctoral Fellowship, Columbia University College of Physicians and Surgeons, New York, NY, 2003-2004

 

Postdoctoral Research Fellowship, Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, 2004-2012

 

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Research Interests:

 

Gene-Environment-Microenvironment Interactions in Melanomagenesis

 

PCMR coverThe overarching goal of my research program is to elucidate the molecular mechanisms of ultraviolet radiation (UVR)-induced melanomagenesis.

 

The major etiological risk factor for the majority of melanomas has long been known to be UVR, yet the underlying mechanisms largely remain elusive. The hunt for melanoma-initiating genes has remained focused on UVR-induced DNA mutations. However, several studies have fueled the notion that mechanisms other than direct DNA damage are also important for UVR-induced initiation and progression of melanoma. To find clues to these mechanisms, we profiled the melanocytic gene expression response to UVR exposure while in their normal skin microenvironment (Nature 469:548). To circumvent the considerable challenge of studying a cell type in vivo that constitutes a tiny fraction of the mammalian skin, we developed a mouse model in which melanocytes can be both imaged in vivo and highly purified by virtue of tetracycline-inducible, melanocyte-specific GFP expression (iDct-GFP mice). This novel mouse model provides an invaluable tool to explore melanocyte and melanoma biology while residing within their natural microenvironment.

 

We have shown that the role of UVR in melanomagenesis involves not only UVR-induced DNA damage, but also how altered gene expression in exposed melanocytes drives interactions with elements of the microenvironment to escape destruction. Our results suggest that UV insult stimulates an intricate interplay between melanocytes and the skin microenvironment. It is clear that the alterations in melanocytic gene expression profile following UVR exposure stem from a combination of the direct UVR-induced effects on melanocytes and microenvironmental cues. We intend to tease out these intrinsic and extrinsic mechanisms to delineate the important molecular players in UVR-induced melanomagenesis.

 

Project 1: Role of the microenvironmental cytokine Interferon-gamma in initiation and progression of UV-induced melanoma


Project 2: The genomic and epigenomic mechanisms of UV-induced melanomagenesis

 

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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

24882515. Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino G, Sodhi A, Chen Q, Gutkind JS, Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry. Cancer Cell 25:6(831-45)2014 Jun 16

24267888. Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, Van Otterloo E, Kim RS, Bergsteinsdottir K, Ogmundsdottir MH, Magnusdottir E, Mishra PJ, Davis SR, Guo T, Zaidi MR, Helgason AS, Sigurdsson MI, Meltzer PS, Merlino G, Petit V, Larue L, Loftus SK, Adams DR, Sobhiafshar U, Emre NC, Pavan WJ, Cornell R, Smith AG, McCallion AS, Fisher DE, Stefansson K, Sturm RA, Steingrimsson E, A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell 155:5(1022-33)2013 Nov 21

23722545. Morishita A, Zaidi MR, Mitoro A, Sankarasharma D, Szabolcs M, Okada Y, D'Armiento J, Chada K, HMGA2 is a driver of tumor metastasis. Cancer Res 73:14(4289-99)2013 Jul 15

22673911. Noonan FP, Zaidi MR, Wolnicka-Glubisz A, Anver MR, Bahn J, Wielgus A, Cadet J, Douki T, Mouret S, Tucker MA, Popratiloff A, Merlino G, De Fabo EC, Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment. Nat Commun 3:(884)2012 Jun 6

22422936. Zaidi MR, De Fabo EC, Noonan FP, Merlino G, Shedding light on melanocyte pathobiology in vivo. Cancer Res 72:7(1591-5)2012 Apr 1

22367038. Debbache J, Zaidi MR, Davis S, Guo T, Bismuth K, Wang X, Skuntz S, Maric D, Pickel J, Meltzer P, Merlino G, Arnheiter H, In vivo role of alternative splicing and serine phosphorylation of the microphthalmia-associated transcription factor. Genetics 191:1(133-44)2012 May

21705455. Zaidi MR, Merlino G, The two faces of interferon-? in cancer. Clin Cancer Res 17:19(6118-24)2011 Oct 1

21392368. Zaidi MR, Hornyak TJ, Merlino G, A genetically engineered mouse model with inducible GFP expression in melanocytes. Pigment Cell Melanoma Res 24:2(393-4)2011 Apr

21248750. Zaidi MR, Davis S, Noonan FP, Graff-Cherry C, Hawley TS, Walker RL, Feigenbaum L, Fuchs E, Lyakh L, Young HA, Hornyak TJ, Arnheiter H, Trinchieri G, Meltzer PS, De Fabo EC, Merlino G, Interferon-? links ultraviolet radiation to melanomagenesis in mice. Nature 469:7331(548-53)2011 Jan 27

21116994. Zaidi MR, Day CP, Merlino G, Fluorescent protein-assisted purification for gene expression profiling. Methods Mol Biol 699:(393-405)2011

18787547. Zaidi MR, Day CP, Merlino G, From UVs to metastases: modeling melanoma initiation and progression in the mouse. J Invest Dermatol 128:10(2381-91)2008 Oct

16885341. Zaidi MR, Okada Y, Chada KK, Misexpression of full-length HMGA2 induces benign mesenchymal tumors in mice. Cancer Res 66:15(7453-9)2006 Aug 1

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FUNDING:

 

National Cancer Institute Transition Career Development Award (K-22)
2012-2015
Principle Investigator
“Pro-tumorigenic role of Interferon-gamma in melanomagenesis: A paradigm shift.”

 

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