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Newsletter of the AAISCR Volume VII Issue 1 November 2016 Mission Statement (Founded in 1994) In this issue Mission Statement The American Association of Indian Scientists in Cancer Research (AAISCR) is a non-profit and a non-political organization established to promote communication among Indian Scientists working in Cancer research specialty areas. The organization will provide infrastructure support in utilization of information and resources available to those who are starting their career as scientists. The organization will focus on the following activities and help scientists in finding answers to the cure of cancer. Editorial Promote scientific interactions by collaborative research Presidential address Exchange of ideas and technologies Share scientific information and experiences Provide honorariums/scholarships for scientific excellence Help translate the scientific discoveries into clinical applications Help identify jobs, postdoctoral fellows and graduate students Scientist Spotlight Research Highlights Meeting Report 2016 Annual Meeting Awardees Announcements Upcoming Meetings Membership application Venue will be announced at a future date & posted to the AAISCR website (www.AAISCR.ORG). Visit our updated web site www.aaiscr.org N-LINK (Newsletter) is a periodic communication of The American Association of Indian Scientists in Cancer Research (AAISCR) Volume VII, Issue I Page 2 American Association of Indian Scientists in Cancer Research (Founded on April 11, 1994) Website: www.aaiscr.org Editorial Board of Directors Aniruddha Ganguly Surinder Batra Dhayan Chandra Gokul M. Das Varsha Gandhi Rita Ghosh Rakesh Kumar Kapil Mehta Neelam Mukherjee Debasis Mondal Harikrishna Nakshatri Subrata Sen Shyam Sharan Sujay Singh Saraswati Sukumar Rajeswar Rao Tekmal Meghana Trivedi Shahid Umar Ratna K. Vadlamudi Arti Patel Varanasi Mansukh Wani President Aniruddha Ganguly Vice President Debasis Mondal Mansukh Wani Treasurer Aniruddha Ganguly Secretary Meghana Trivedi Anjana Saxena N-LINK (Newsletter) Harikrishna Nakshatri (Chair) Rita Ghosh Arti Patel Varanasi Neelam Mukherjee Debasis Mondal Kapil Mehta Subrata Sen Rajeshwar Rao Tekmal www.aaiscr.org As I write this editorial for the first time, many thoughts came to my mind and the major one being how hard it is to write a general article than a scientific article. During well-attended and highly successful annual AAISCR meeting in New Orleans, the board decided to restart the newsletter twice a year. The main purpose was to engage AAISCR community through out the year. We are in the era of news overload through both print and social media. Average number of business-related emails we receive now is 121, which is likely to increase to 140 by 2018. There is a natural tendency to press “delete” button after receiving an email with an attachment. We hope our newsletter will not meet the same fate and the information provided are useful for young investigators for networking and to establish a mentoring relationship with more experienced investigators. Another goal of this newsletter is to highlight ground breaking and paradigm shifting work done by investigators of Indian origin. Few of us may find overall scientific premise of the study appealing while others may find the work of practical use in their research. I believe two articles highlighted in this issue meet both criteria. We apologize for not including several other worthy publications in this section and we welcome contributions from the community in future newsletters. Please contact me or editorial board members if you would like to contribute. Many of us left our motherland many years ago but still follow the events back home. We feel proud when Indian cricket team or any other sportsperson does well at international events. Our feelings are similar when one of our colleagues receives national and international recognition for their contributions to science. In addition to recognizing distinguished scientists at our annual event, we are highlighting their success in the newsletter. We are very pleased to highlight career of Dr. Rakesh Jain, recipient of 2013 US National Medal of Science from President Obama as well as a member of all three branches of US National Academies. Despite his busy schedule, he took time to provide information we requested. Our editorial team worked hard in putting together this newsletter and made my task very easy. I sincerely thank all of them for their hard work. We appreciate your comments and contributions to further improve the newsletter. ~ Harikrishna Nakshatri, Ph.D. Newsletter of the AAISCR Page 3 Presidential Address Dear Colleagues: It is an honor and privilege to serve AAISCR as the President. For the last 24 years AAISCR has been serving community of cancer researchers with integrity, loyalty, generosity and respect, and this tradition will continue for many years to come. It has been realized that AAISCR best serves by connecting scientists of similar interests, promoting collaborations, exchanging scientific ideas, mentoring, and recognizing scientific talents via various award mechanisms. As you know, we are experiencing an unprecedented explosion of knowledge and discoveries in almost every area of cancer research. In order to excel in this environment, one might find benefit of collaborating with investigators of common interest to bring technologies and skill sets needed to achieve specific scientific goals. In this regard, AAISCR is a platform to get connected with cancer researchers from a variety of research backgrounds. In addition, AAISCR presents an opportunity to discuss grant-related questions and NIH funding initiatives with NIH Program Directors attending AAISCR Annual Meetings as panel members for the grant-related discussion forum. We understand that researchers and students coming from outside the USA with diverse backgrounds may experience challenges at various levels including coping with the new environment in addition to acquiring knowledge and learning new skills and technologies in a fast-paced environment. To address these challenges, AAISCR has developed “mentoring program” for researchers. Please visit our web site, www.aaiscr.org, to learn about the program and use this opportunity to advance your career. We want to know that there are many experienced and well-established investigators available and willing to offer you guidance at different levels. In an effort to appreciate research excellence and encourage new and established investigators, AAISCR Award Committees have been recognizing achievements of American Indian Scientists or otherwise through various awards. These awards are testament of scientific excellence. We encourage you to take an active role in this organization and certainly welcome your suggestions to make this organization better and stronger. This is your organization, and we need your help to better serve the AAISCR community. Please let me (email: [email protected]) know today rather than tomorrow if you are interested to play an active role and we will be glad to get you involved. It is with great pleasure I inform that we have revived periodic release of AAISCR News Letters (N-Link) is an effort to connecting with the community of AAISCR scientists in between annual meetings and sharing useful information and news, and keeping the community updated on year-round activities of AAISCR. Many thanks to our News Letter team for their efforts to publish this issue of the N-Link. Let us work together to advance cancer research and patient care. It is an endeavor worth pursuing. With best wishes and regards, Aniruddha Ganguly, Ph.D. Newsletter of the AAISCR Page 4 Scientist Spotlight Rakesh K. Jain, Ph.D., A. W. Cook Professor of Radiation Oncology (Tumor Biology), Director, E.L. Steele Laboratories, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, 100 Blossom Street, Cox 7, Boston, MA 02114. It is highly appropriate to list few of his many accomplishments before describing his career path. In 2016, Dr. Jain received the US National Medal of Science from President Obama (awarded on May 19, 2016): “For pioneering research at the interface of engineering and oncology, including tumor microenvironment, drug delivery, and imaging; and for discovering groundbreaking principles guiding the development and novel use of drugs for cancer and non-cancerous diseases” Rare distinction of being a member of all three branches of the U.S. National Academies (the National Academy of Medicine, the National Academy of Engineering, and the National Academy of Sciences ) and the American Academy of Arts and Sciences. Selected as one of the top 1% cited researchers in Clinical Medicine by Thomson-Reuters Web of Science (www.highlycited.com) with 650 publications, >76,000 citations, and h-factor=133 One of 50 Oncology Luminaries chosen on the occasion of the 50th anniversary of the American Society of Clinical Oncology Honorary doctorates from Duke University, Durham, North Carolina, KU Leuven, Belgium, and IIT-Kanpur, India 75 awards from engineering and medical professional societies/institutions, including a Guggenheim Fellowship, Humboldt Senior Scientist Award, 2012 American Society of Clinical Oncology (ASCO) Science of Oncology Award, 2014 American Association of Cancer Research (AACR) Princess Takamatsu Memorial Lectureship Award A mentor to more than 200 Master's, doctoral, and postdoctoral students from over a dozen different disciplines 1993-2000 and 2015-2022 Outstanding Investigator Award, National Cancer Institute, National Institutes of Health Dr. Rakesh Jain is a pioneer in the area of tumor microenvironment. He was committed to studying mechanisms associated with overcoming drug delivery barriers in solid tumors in an era when such research was not at the frontline. Dr. Jain integrated knowledge from engineering, optics, mathematics, physiology, immunology, and cellular and molecular biology to understand tumor biology. This multidisciplinary approach has led to groundbreaking discoveries in tumor biology, drug delivery, in vivo imaging, bioengineering, and bench-to-bedside translation. His pioneering work established the new paradigm that normalization of vasculature is essential for effective treatment of malignant and non-malignant diseases that afflict more than 500 million of people worldwide, and formed the basis of more than25 clinical trials and multiple drug approvals in the United States and worldwide. Newsletter of the AAISCR Page 5 A courageous journey from a chemical engineer to a world-renowned cancer researcher- : Dr. Jain received his chemical engineering degree from IIT, Kanpur in 1972, MS and PhD degrees in 1974 and 1976 in chemical engineering from the University of Delaware. He served as assistant professor of chemical engineering at Columbia University (1976 to 1978), and as assistant (1978-79), associate (1979-83) and full professor (1983-1991) of chemical engineering at Carnegie Mellon University. He spent his 1983-84 sabbatical year as a Guggenheim Fellow in the departments of chemical engineering at MIT, bioengineering at UCSD and radiation oncology at Stanford; and his 1990-91 sabbatical as a Humboldt Senior Scientist-Awardee at the Institute of Pathophysiology of University of Mainz, and the Institute of Experimental Surgery of University of Munich. As of 1991, Dr. Jain is the Andrew Werk Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School, and Director of Edwin L. Steele Laboratories of Tumor Biology at Massachusetts General Hospital. Dr. Jain explained his journey in an interview, published in Campuskrant, after receiving his honorary degree from KU Leuven, Belgium in 2015, stating: In those days, Indians had the reputation of being very good in mathematics but not so good at experiments; as a young doctoral researcher, I wanted to change that stereotype. He got the chance to change the stereotype in 1974 when he came in contact with the well-known tumor pathophysiologist Pietro Gullino, MD, at the National Cancer Institute. He was curious to know whether anyone had systematically looked into how much of a given drug actually made it into the tumor and the answer was “no”. That was the beginning of his quest to understand the tumor microenvironment, vasculature, and how abnormalities in the microenvironment affect drug delivery and efficacy. His engineering background became very handy, as there were no tools to study this complex problem and the next twenty years of his career were dedicated for developing cutting-edge tools to decipher the tumor microenvironment. These tools enabled him to put forward a radical concept that normalizing tumor vasculature is essential for effective drug delivery, particularly in the era of “hot” anti-angiogenic therapy and multi-billon dollar investments by industry in developing anti-angiogenesis therapies. Sounds familiar? Even with these innovative tools and ideas - he had difficulty in getting funded because he was swimming against the tide. He says:Especially in the early years, when what I was doing was 180 degrees from what the field was trying to do at the time. Today, there are still skeptics. But I cannot blame them because it’s human nature. Whether it’s art or science, in every human endeavor any time someone proposes a radically new idea it’s never immediately embraced. It is discouraging but one should not give up. I always tell my students that. Don’t be afraid to cross boundaries. My advice is to get out of your comfort zone. I’m proud that I took a chance as a chemical engineer. After completing his middle school in Lalitpur, UP, where he was born on December 18, 1950, Jain attended Model High School in Jabalpur, MP (1963-66). After a gap year because of being underage, he attended the Indian Institute of Technology in Kanpur (1967-72). Rakesh Jain is the oldest of ten children – five boys followed by five girls. Even after being in the US for 44 years, Jain is very close to his siblings and their families in India. Jain is married to Jacqueline A. Samson, PhD, who is also on the Harvard Medical School faculty. They have 14 year old twin daughters. Dr. Jain: I am very grateful to my family members for their love, inspiration, patience and support. Newsletter of the AAISCR Page 6 Research Highlights from Scientists of Indian Origin In this section, we highlight outstanding articles that were published recently by Indian scientists. We apologize for not citing other excellent articles published by our scientists due to space limitation. Athuluri-Divakar SK, Vasquez-Del Caprio RV, Dutta K, Baker SJ, Cosenza SC, Basu I, Gupta YK, Reddy MVR, Ueno L, Hart JR, Vogt PK, Mulholland D, Guha C, Aggarwal AK, and Reddy EP. A small molecule RAS-mimetic disrupts Ras association with effector proteins to block signaling. Cell 165, 643-655, 2016 (PMID:27104980). Activating mutations in Ras proto-oncogene are observed in multiple cancers including deadly pancreatic and lung cancers. Decades of research by academia and industry have failed to come up with a drug that can target activated Ras protein. Ras lacks druggable pockets or cavities. NCI recently established a “Manhattan Project” focused on developing drugs targeting Ras and has earmarked millions of dollars. In the meantime, in New York, Dr. Reddy and his colleagues were quietly developing drugs that may target Ras. Although not apparent in the paper, it appears that their discovery is somewhat accidental, nonetheless significant. Their efforts were to identify targets of the drug rigosertib, which is in Phase III clinical trial for myelodysplastic syndrome. Rigosertib was initially developed as an inhibitor of PLK1. In affinity purification studies, rigosertib bound preferentially to Ras binding domains (RBD) containing proteins including Ral-GDS, Raf, and PI3K. Subsequent worked showed the ability of rigosertib to inhibit heterodimerization between cRAF and B-RAF. Furthermore, the drug reduced the activity of both wild type and mutant K-Ras. The drug had therapeutic effects in K-rasG12D genetically engineered mouse model of pancreatic cancer. Critically, in ongoing clinical trials of patients with myelodysplastic syndrome, better response was noted in patients with monosomy of chromosome 7 and trisomy of chromosome 8, two cytogenetic abnormalities that are associated with Ras activation. Very promising finding with immediate translational potential! Mou H, Vinarsky V, Tata PR, Brazauskas K, Choi SH, Crooke AK, Zhang B, Solomon GM, Turner B, Bihler H, Harrington J, Lapey A, Channick C, Keyes C, Freund A, Artandi S, Mense M, Rowe S, Engelhardt JF, Hsu Y, and Rajagopal J. Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells. Cell Stem Cell 19, 217-231, 2016 (PMID:27320041) Replenishment of non-transformed primary epithelial cells for in vitro functional studies has proven extremely difficult as primary cells undergo replicative senescence after few divisions. Few advances to grow such cells on irradiated mouse fibroblasts with supplemented ROCK inhibitors are reported (American Journal of Pathology 180:599-607-PMID 22189618). Dr. Rajgopal and his colleagues have developed an innovative method to grow primary epithelial cells by reprogramming the signaling pathways without the need for feeder layer. Mou et al. successfully replicated functional airway epithelial cells on plates pre-coated with 804G-conditioned medium when supplemented with dual inhibitors of TGFb/BMP. More so this technique is applicable to epithelial cells derived from all three germ layers. Although the cells grown under this condition are still enriched for basal epithelial cells instead of luminal cells from which cancers typically originate, the technique has the potential to change the way we validate the function of genes mutated in cancer. Volume VI, Issue I-II Page 7 23rd AAISCR Awards Recognized Established and Young Indian Scientists for Excellence in Cancer Research The 23rd Annual Meeting of American Association of Indian Scientists in Cancer Research (AAISCR, Inc.) was held on April 18, 2016 in a ballroom at the Holiday Inn DowntownSuperdome, New Orleans. The meeting was attended by many well-known scientists including Dr. Shankar Adhya (Senior investigator at the National Cancer Institute, an elected member of the National Academy of Sciences, and Fellow of the American Academy of Arts and Sciences), and bright and energetic young scientists. AAISCR Lifetime Achievement Award was given to a scientist who has made significant fundamental contributions to cancer research including treatment, either through a single scientific discovery or a body of work, and must have had a lasting impact on cancer research and demonstrated a lifetime commitment to progress against cancer. Dr. Sankar Mitra (Full Member and Professor at Houston Methodist Hospital and Research Institute, TX) received Lifetime Achievement Award for many of his fundamental discoveries in the area of repair of alkylation and oxidative DNA damage. Dr. Mitra and his colleagues codiscovered the suicide enzyme for repairing mutagenic O-6 alkylguanine, and were the first to clone its human ortholog and named MGMT (O-6-Methylguanine-DNA-methyltransferase). MGMT methylation status has been routinely used in making clinical decisions. His group discovered and characterized two additional human DNA glycosylases which Dr. Mitra named NEIL1 and 2. These along with OGG1 and NTH1 provide major repair activity for oxidative base damage in nuclear and mitochondrial genomes. Dr. Raju S. K. Chaganti (Tenured Member and Professor, Memorial Sloan-Kettering Cancer Center, New York, NY) received Lifetime Achievement Award for his lifetime studies on the genetics of human cancer focusing on leukemia, B-cell lymphoma, and adult male granulose cell tumors. One of his contributions is the discovery of novel chromosomal translocations and cloning and characterization of deregulated genes at the breakpoints and their role in biology and clinical behavior of the disease. This is illustrated by identification of the translocations involving the promiscuously rearranging chromosomal band 3q27 in diffuse large B cell lymphoma, followed by cloning and characterization of the BCL6 gene from that chromosomal site, and evaluating its clinical importance, the latter by correlative analysis of a large group of patients. BCL6 is now recognized as a key gene in the regulation of normal B-cell development in the germinal center, and routinely used for making clinical decisions. AAISCR Outstanding Scientist Award recognized novel, and significant biomedical research which has led to important contributions in basic and translational cancer research, cancer diagnosis, cancer prevention, or treatment of patients with cancer. Volume VI, Issue I-II Page 8 Dr. Adhip P. N. Majumdar (Professor, Wayne State University School of Medicine, MI) was awarded for his contributions in elucidating the patho-physiology of age-related changes in the gut mucosa specifically those which lead to the development of malignancy. With respect to the involvement of cancer stem cells (CSCs) in gastrointestinal carcinogenesis, Dr. Majumdar’s group was the first to demonstrate that age-related increase in adenomatous polyps in the colon was not only associated with activation of epidermal growth factor receptor (EGFR) but also increase in CSCs in the colonic mucosa suggesting a relationship between EGFR and CSCs in the aging colon. Dr. Shivendra Singh (Professor, University of Pittsburgh, PA) was awarded for his contributions in cancer prevention research. His studies with phenethyl isothiocyanate (PEITC) have shown, for the first time that PEITC is bioavailable in mouse prostate after dietary administration. More importantly, dietary PEITC administration significantly decreased prostate cancer incidence and burden in a transgenic mouse model. Mechanistic studies revealed apoptosis induction and angiogenesis suppression in prostate cancer chemoprevention by PEITC. These observations provide scientific basis for clinical evaluation of PEITC for prevention of prostate cancer. Dr. Singh’s group is also the first to provide critical preclinical data supporting cancer chemopreventative potential of broccoli-constituent sulforaphane and its potential application for prostate cancer prevention. AAISCR rewarded excellence in research conducted by young investigators (junior faculty, postdoctoral fellow and graduate student) to encourage their research activities in cancer and cancerrelated biomedical research. This year Young Investigator Awards were presented to the following bright budding scientists for their outstanding research presented at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans. In the Postdoctoral Fellow/Junior Faculty category, Dr. Girijesh K. Patel (University of South Alabama) was awarded for his research presentation entitled “Chemotherapy-induced exosomal secretion promotes chemoresistance in pancreatic cancer cells”, and Dr. Suryavathi Viswanadhapalli (University of Texas Health Sciences Center at San Antonio) was awarded for her research presentation on “The role of proto-oncogene PELP1 in breast cancer stem cell maintenance and therapy resistance”. In the Graduate Student category, Saswati Karmakar was awarded for her research presentation entitled “hPaf1/PD2 interacts with OCT3/4 in maintenance of the self-renewal process of ovarian cancer stem cells”, and Suprit Gupta was awarded for his research presentation entitled “Alterations in endothelin axis during pancreatic acinar to ductal metaplasia”. Both are graduate students at the University of Nebraska Medical Center, Omaha, NE. AAISCR awards are testament of scientific excellence that helps promote career development, and mark distinction in their scientific career. AAISCR appreciates high quality reproducible research that may become meaningful overtime to the cancer research community. Newsletter of the AAISCR Page 9 Awards were presented to post-doctoral fellows and graduate students who presented their work at the annual American Association for Cancer Research meeting. Fourteen postdoctoral fellows and 8 graduate students competed for these awards and six member judging committee reviewed their abstracts and selected winners. Postdoc Category Graduate Student Category Suryavathi Viswanadhapalli Saswati Karmakar UT Health Science Center at San Antonio [email protected] University of Nebraska Medical Center [email protected] Girijesh K. Patel Suprit Gupta University of South Alabama [email protected] Fred and Pamela Buffet Cancer Center University of Nebraska Medical Center [email protected]. Announcements 24th AAISCR Annual Meeting will be held on Monday April 3, 2017 in Washington DC. The venue will be announced later and posted on our website (www.aaiscr.org) as well. We look forward to seeing you and your friends and colleagues at the meeting. In a couple of months, you will receive an announcement from us to submit your accepted for presentation AACR abstract to the AAISCR Young Investigator Award Committee for consideration of an award. We request principal investigators to encourage their young investigators, including postdoctoral fellows and graduate students, to submit their abstracts on time. Details will be available at the AAISCR website (www.aaiscr.org). The AAISCR Senior Scientist Awards Committee is engaged in selecting Lifetime Achievement and Outstanding Scientist awardees for 2017. Newsletter of the AAISCR Page 12 List of upcoming meetings of interest (in India) 2nd Indian Cancer Congress 08 - 12 November, 2017 | Bengaluru http://www.indiancancercongress2017.com Evidence Based Management of Cancers in India Tata Memorial Hospital, Mumbai. 24th to 26th February 2017 https://tmc.gov.in/m_events/Events/conference 36th Annual Conference of Indian Association for Cancer Research The 21st Century - War on Cancer Amala Cancer Research Centre Thrissur - Kerala February 9-11, 2017 Organizing Secretary, Dr. Ramadasan Kuttan 9447123071 email: [email protected] World Congress on Drug Discovery & Development-2016 November 23-25, 2016 J.N.TATA AUDITORIUM INDIAN INSTITUTE OF SCIENCE BENGALURU, INDIA. http://www.drugdiscoveryconference.org Volume VII, Issue I Page 14 Happy Thanksgiving Request for articles: The editorial board welcomes your submission for our newsletter. You can write on immigration, finances, career development, request for reagents, chemicals, availability of positions, notable publications, achievements, appointments, promotions, significant accomplishments of the members, technical tips, availability of various career opportunities, etc. Please e-mail articles to Dr. Harikrishna Nakshatri ([email protected]), Dr. Arti Varanasi ([email protected]) and Dr. Debasis Mondal ([email protected]).