Rafael Fridman, Ph.D.
540 E. Canfield
8200 Scott Hall
Detroit, MI 48201
Our research goal is to understand the molecular and cellular mechanisms that facilitate tumor cell invasion and metastasis. To invade tissue barriers (extracellular matrix), metastatic tumor cells activate migratory and invasion programs that turn on genes involved in cell adhesion and proteolysis. Our lab is focusing on unveiling the cross talk between the discoidin domain receptors (DDRs), a unique set of receptor tyrosine kinases (RTKs) that are specifically activated in response to collagen, and the matrix metalloproteinases (MMPs), a family of proteases known to degrade collagen. The focus of our research is to understand DDR signaling and function in breast and prostate cancer. In breast tissues, we are investigating the role of DDRs in normal mammary gland morphogenesis and function and in cancer development, specifically DDRs' role in the transition from in situ to invasive carcinoma. In prostate cancer, our focus is unveiling the contribution of DDRs to the survival of prostate cancer cells in the bone microenvironment, the major site of prostate cancer metastasis. We are also investigating how proteolysis of the collagen matrix by MMPs regulates DDR phosphorylation and signaling in normal and malignant cells. Our hypothesis is that a cross between MMP activity and DDR signaling contributes to tumor cell invasion and metastasis. To address this hypothesis, we utilize a comprehensive variety of biochemical, structural, and cellular approaches, animal models of cancer progression and knockout mice.
Fridman R. Preface - Matrix metalloproteinases. Biochim Biophys Acta. 2017;S0167-4889:30193-3.
Mainetti LE, Zhe X, Diedrich J, Saliganan AD, Cho WJ, Cher ML, Heath E, Fridman R, Kim HR, Bonfil RD. Bone-induced c-kit expression in prostate cancer: a driver of intraosseous tumor growth. Int J Cancer. 2015;136:11-20.
Koh M, Woo Y, Valiathan RR, Jung HY, Park SY, Kim YN, Kim HR, Fridman R, Moon A. Discoidin domain receptor 1 is a novel transcriptional target of ZEB1 in breast epithelial cells undergoing H-Ras-induced epithelial to mesenchymal transition. Int J Cancer. 2014 Aug 23.
D'Angelo RC, Liu XW, Najy AJ, Jung YS, Won J, Chai KX, Fridman R, Kim HR. TIMP-1 via TWIST1 Induces EMT Phenotypes in Human Breast Epithelial Cells. Mol Cancer Res. 2014;12:1324-33.
Mainetti LE, Zhe X, Diedrich J, Saliganan AD, Cho WJ, Cher ML, Heath E, Fridman R, Kim HR, Bonfil RD. Bone-induced c-kit expression in prostate cancer: A driver of intraosseous tumor growth. Int J Cancer. 215;136:11-20.
Fu HL, Valiathan RR, Payne L, Kumarasiri M, Mahasenan KV, Mobashery S, Huang P, Fridman R. Glycosylation at Asn211 regulates the activation state of the discoidin domain receptor 1 (DDR1). J Biol Chem. 2014;289:9275-87
Dilly AK, Ekambaram P, Guo Y, Cai Y, Tucker SC, Fridman R, Kandouz M, Honn KV. Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-κB. Int J Cancer. 2013;13:1784-91
Fu HL, Sohail A, Valiathan RR, Wasinski BD, Kumarasiri M, Mahasenan KV, Bernardo MM, Tokmina-Roszyk D, Fields GB, Mobashery S, Fridman R. Shedding of discoidin domain receptor 1 by membrane-type matrix metalloproteinases. J Biol Chem. 2013;288:12114-29.
Nangia-Makker P, Raz T, Tait L, Shekhar MP, Li H, Balan V, Makker H, Fridman R, Maddipati K, Raz A. Ocimum gratissimum retards breast cancer growth and progression and is a natural inhibitor of matrix metalloproteases. Cancer Biol Ther. 2013;14:417-27.
Fu HL, Valiathan RR, Arkwright R, Sohail A, Mihai C, Kumarasiri M, Mahasenan KV, Mobashery S, Huang P, Agarwal G, Fridman R. Discoidin domain receptors: unique receptor tyrosine kinases in collagen-mediated signaling. J Biol Chem. 2013;288:7430-7
Education and Training
PhD (1986): Hebrew University, Jerusalem, Israel
Post-Doc (1986-1991): National Institutes of Health, Bethesda, Maryland