If I can do it, so you can!

Dr. Suresh K.Rayala

This is aimed to provide inspiration and guidance to those students who choose to take Biology as their major at Graduate level.

Currently, I am working as Assistant Professor in the Department of Molecular and Cellular Oncology at MD Anderson Cancer Center, Houston, USA and has made very important contributions in the field of cancer as evidenced by several peer reviewed publications in International journals. My research focuses on understanding the molecules as well as the molecular mechanisms underlying tamoxifen resistance, study the bridging and interplay between growth factor receptor and estrogen receptor pathway in the development of tamoxifen resistance, non-genomic actions of estrogen receptor. I came to USA during June 2003 and with in these four years, I have made excellent progress in my career which definitely has added to the advancement of cancer field.

Coming to my education background, I did my schooling and college from Andhra Pradesh. After finishing my post graduation in Biochemistry, I did my Ph.D in Cancer Biology from Cancer Institute, Adyar, Chennai during 1999-2002 in the area of breast cancer. During my Ph.D, I generated and characterized monoclonal antibody against C-erbB-2 oncoprotein and tested its efficacy as a tumor targeting agent by Immunoscintigraphy in nude mouse models. Results from my research work clearly suggested that monoclonal antibody which I generated might prove useful to identify tumors with overexpression of C-erbB-2. I clearly demonstrated the potential application of this monoclonal antibody for in vivo diagnosis of occult malignancies in animal tumor models with overexpression of C-erbB-2, which are often associated with poor prognosis and early recurrence and might have future therapeutic application in the treatment of these cancers. During this tenure, I was awarded Young Scientist award twice. Immediately after finishing my Ph.D in June 2002, I joined as a Scientist in Antibody Development wing at Shantha Biotechnics Ltd, Hyderabad, INDIA and worked there from July 2002 – May 2003. There I was involved in development of monoclonal and polyclonal antibodies against various tumor associated antigens and leading a research team. During this period of less than One year, my team developed several monoclonal and polyclonal antibodies. One of the antibody against Cathepsin D developed by my group is commercialized by an US based company. This is a great achievement as a Group leader and a land mark in my career, since most US companies commercialize products that are highly reliable and good. Then during May 2003, I was offered Post Doctoral Fellowship from Professor Rakesh Kumar’s lab at MD Anderson Cancer Center and moved to Houston in June 2003. MD Anderson Cancer Center is one of the world's most respected centers devoted exclusively to cancer patient care, research, education and prevention. Here, most of my research work focused on identifying ways to combating tamoxifen resistance. Tamoxifen, a nonsteroidal antiestrogen has been the preferred antiestrogen hormonal treatment for breast cancer for the past three decades. It is an established therapy which is relevant to the treatment of all stages of breast cancer. However, resistance to tamoxifen frequently develops with extended treatment. This resistance is a serious obstacle in the management of breast cancer. Scientists do not yet have a clear understanding of the molecular mechanisms that underlie the failure of anti-estrogenic action of tamoxifen (tamoxifen- resistance) or of the breast cancer progression to more invasive phenotypes or the development of ER-negative breast cancer. p21-activated kinases (PAKs) are serine/threonine kinases that function as downstream nodes for various oncogenic signalling pathways.Emerging data suggests that elevated PAK1 expression in premenopausal breast cancer patients correlates well with a lack of tamoxifen response despite the presence of ER-alpha expression.

I continued to search how exactly PAK regulates ER activity with a particular focus on ER structural consideration and tamoxifen action. I found that tamoxifen led to upregulation of ER target genes in PAK1 overexpressing cells and increased Pak1-ER interaction in tamoxifen-resistant but not in tamoxifen-sensitive cells. Further, i identified a mechanistic role of ER-Serine 305 activation in triggering a subsequent phosphorylation of Serine 118, presumably due to conformational changes. I further continued my passion with PAK1, and our groups findings were validated directly in the human specimens in collaboration with a major group from Sweden. This recently completed study of 403 primary breast tumor samples isolated from premenopausal patients who received either two years of adjuvant tamoxifen therapy or no treatment revealed a strong correlation between the high levels of PAK1 expression and lack of tamoxifen response in tumors that expressed ER. Collectively, my research embarked on an important problem of cancer research. The past four years of my research work along with several of my colleagues in Professor Kumar’s lab have put PAK1 on the scientific map of hormone resistance and now providing novel therapeutic approaches targeting PAK regulation of estrogen receptor-alpha (ER) transactivation functions. Our group findings also prompted a further investigation of how nuclear signaling by PAK1 may affect estrogen's action and whether tamoxifen resistance might be prevented or reversed by PAK1 inhibition.

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I spend most of my time in laboratory working on my experiments. I feel very lucky to have made a tiny contribution to cancer research within a short span of four years. Every project I do, is a challenge and I take pleasure in taking these challenges. Everyday is a learning experience for me and I strive and work hard to achieve what I want. Till now, I have authored more than 40 papers in International Journals and am one of the leading Cancer Researchers in the field. I was inspired and encouraged by lot of people during this 9 years of my research on cancer, especially by Ph.D. guide Dr.T.Raj Kumar, Director of Cancer Institute, Chennai, and now by Professor Kumar, my Current supervisor and Deputy Chairman at the Department of Molecular and Cellular Oncology, MD Anderson Cancer Center.

Since I was of the impression that Biology has no future, I just want to get it to the notice of all youngsters about the facts. I have gone thorough very tough times in my career, but did not loose my confidence which kept me on track. With the experience I had gained, I plan to start my independent research lab in INDIA which is my ultimate dream. I am sure that I will be a successful Cancer Researcher in future. Finally, all this indicate that, it does not matter in which field you are, what matters is what you do. I will be very happy to provide any support and assistance to young biology graduates.