User:Mahendragbc

 Mahendra Singh (scientist) 

Mahendra K. Singh, Ph.D., is a researcher at Miller School of Medicine University of Miami in Miami (1). Singh was born in a remote village of northern India in a family of farmers. After completing his Masters degree in Biochemistry, Singh developed interest in cancer research and joined a Ph.D. program at a premier medical school in India where he worked on molecular epidemiological aspects of gallbladder cancer which is almost an endemic disease in northern part of India. Singh was able to secure a prestigious postdoctoral fellowship at a premier Institute of Cancer Research in the United States in the year 2003 under mentorship of Dr. Erica Golemis, a world leader in the field of cell signaling and systems biology. His current research focuses on the adhesion signaling pathways with special focus on gallbladder cancer (1).

Dr. Singh's contribution to science:

1. Dr. Singh discovered a novel protein HEPL, also known as CASS4 as the 4th member of the CAS protein family. In this work, Dr. Singh demonstrated a direct interaction between CASS4 and FAK and how this interaction between these two signaling proteins regulates cellular adhesion and metastatic behavior of cancer cells. It is becoming apparent to further study regulatory role of CASS4 in the metastasis pathways in the context of other CAS proteins, by developing various model systems including animal model for deregulated CASS4 expression. (https://en.wikipedia.org/wiki/CASS4) (2)

2. Dr. Singh, along with others, helped establish NEDD9 as a cancer cell-intrinsic protein that contributes to mammary tumor development in the MMTV-PyMT mouse model. This study provides the first in vivo evidence of a role for NEDD9 in breast cancer progression, and suggests that NEDD9 expression may provide a biomarker for tumor aggressiveness (3).

3. Dr. Singh demonstrated that constitutive absence of an adapter protein NEDD9/HEF1 in a genetic mouse model of mammary tumors induced defects in cell cycle associated with reduced function of Aurora Kinase A and a more aggressive tumor phenotype. The absence of NEDD9 also caused a persistent deficiency in Src activation and influences the susceptibility of mammary cancer cells to dasatinib, a drug targeting Src kinase, which demonstrates the potential of NEDD9 as a biomarker for clinical response (4).

4. Early on in his scientific career, Dr. Singh identified a novel polymorphic variant of apolipoprotein B as a genetic predisposing factor associated with gallbladder cancer (GBC) and provided one of the first evidences as to how a single nucleotide polymorphic variant (not a mutant) increases the risk for developing GBC which is the commonest biliary tract malignancy with no effective therapy available. Singh was first from India to have reported mutation of K-ras oncogene in about one third of the patients with GBC, first report of its kind from India where GBC is 3rd most common gastrointestinal malignancy (5,6).

Singh serves on the editorial boards of several scientific journals of international repute and also serves as reviewers for several journals.

References:

(1) https://umiamihealth.org/labs-and-researchers/people/sylvester/mahendra-k-singh-phd

(2) https://en.wikipedia.org/wiki/CASS4

(3) Izumchenko E, Singh MK, Plotnikova OV, Tikhmyanova N, Little JL, Seo S, Kurokawa M, Egleston BL, Klein-Szanto A, Pugacheva EN, Hardy RR, Wolfson M, Connolly DC, Golemis EA. NEDD9 promotes oncogenic signaling in mammary tumor development. Cancer Res 2009 Sep 15;69(18): 7198-206.

(4) Singh MK, Izumchenko E, Klein-Szanto A, Egleston BL, Wolfson M, Golemis EA. Enhanced genetic instability and dasatinib sensitivity in mammary tumor cells lacking Nedd9. Cancer Res 2010 Nov 1;70(21):8907-16.

(4) Singh MK, Pandey UB, Ghoshal UC, Srivenu I, Kapoor VK, Choudhuri G, Mittal B. Apolipoprotein B-100 XbaI gene polymorphism in gallbladder cancer. Hum Genet. 2004 Feb; 114(3):280-3.

(5) Singh MK, Chetri K, Pandey UB, Kapoor VK, Mittal B, Choudhuri G. Mutational spectrum of K-ras oncogene among Indian patients with gallbladder cancer. J Gastroenterol Hepatol. 2004 Aug;19(8):916