Cell Press, Current Biology Magazine-Dr. Anindya Dutta

AnindyaDutta-MBBS-PhD

Anindya Dutta started out to be a physician, earning his MBBS degree from Christian Medical College, Vellore, India. After a year of residency in medicine he sought out lab research at the Indian Institute of Chemical Biology in Kolkata. Recognizing the need for more formal training in basic research, he went to Rockefeller University in New York City to do his PhD with one of the pioneers of retroviruses and oncogenes, Dr. Hidesaburo Hanafusa. A postdoctoral fellowship with Dr. Bruce Stillman at Cold Spring Harbor Laboratory introduced him to the cell cycle, following which he did a short residency in Anatomic Pathology at Brigham and Women’s Hospital, Harvard Medical School. Dr. Ramzi Cotran, the chair of Brigham’s Pathology department, was legendary for his ability to nurture research. He, along with Dr. Peter Howley (Chair of Pathology at Harvard), promoted Anindya to Assistant Professor of Pathology and head of his own lab. In 2003, another very effective chair, Dr. Joyce Hamlin, wooed him to the University of Virginia, where he has been ever since, eventually succeeding Dr. Hamlin as Chair of Biochemistry and Molecular Genetics in 2011.

Please take a few minutes to describe your career path.

I grew up in a town called Kulti in the iron and coal belt of India. My father had found himself on the wrong side of the
religious divide that accompanied the Partition of British India, and so moved to the Indian state of West Bengal from
East Pakistan (now Bangladesh). He managed to get a degree in engineering after migrating as a refugee. Education
was highly valued in our home, and as the eldest son of the family I was expected to become a professional who could make a living, either an engineer or a doctor. Contentious left-wing politics in my state, however, completely paralyzed the higher education institutions and I had strong motivation to get out of West Bengal. Luckily for me, I got into CMC, Vellore, in a town that was a two-and-a-half day train journey from my home. CMC became a home away from home, and drove into its students’ heads that we had to do something excellent with our lives and careers. The medical school produced not only great physicians but also a significant amount of research. Two fellow students, both now scientists of some repute (Ashok Venkitaraman at Cambridge and Shiv Pillai at Harvard), inspired me to check out basic research after finishing medical school. I fell in love with the discipline, and so here I am after a PhD,
postdoctoral fellowship and a few years of internship/residency, running a basic science lab in a town probably smaller than the one I grew up in.

How do you describe your area of research?

I have been continuously interested in the basic science of cell proliferation and cancer and have become engrossed in a variety of topics. I started out (during my PhD) studying regulation of gene expression by tyrosine kinase oncogenes. During my postdoctoral fellowship I was introduced to the cell cycle and DNA replication, so I established my lab in
that area, working on p21and CDKs, on human DNA replication initiation factors and control of replication and re-replication. I continue to have an active program in this area, having worked on the genomics of replication initiation and replication timing, on the regulation of various factors involved in genome stability by CRL4/ Cdt2 ubiquitin ligase and now on the way in which replication and repair factors (their overexpression or loss) impact chemotherapy of cancers with drugs like doxorubicin and cisplatin. However, results from the lab were edging my interest towards noncoding RNAs. This interest stemmed from a control experiment where we had made a mismatched siRNA that was
not supposed to inhibit the expression of the target, p21, and yet it was quite robust at doing so. We realized that a
mismatched short RNA could decrease the expression of a target, somewhat similar to what was then called smalltemporal RNAs (stRNAs) in C. elegans, and now known as microRNAs. The start-up funds that I received upon
my move to UVA allowed me to develop a parallel research program on microRNAs in muscle cell differentiation
and in cancer. This area has now taken over nearly half my lab and has developed organically into the study of
long noncoding RNAs.

So I am currently very interested in at least three very hot areas of research. The DNA work has led my lab to discover that normal mammalian cells (and those from chickens, worms and fl ies) have tens of thousands of extrachromosomal circles of DNA, mostly between 100–400 bases long, that we call microDNAs. We are puzzled by their weirdness, ubiquity and abundance and are searching for their function. The microDNAs occasionally come with accompanying chromosomal microdeletions that are somatically mosaic and could have interesting implications for normal development and disease. In parallel, while sequencing microRNAs we discovered a novel family of short RNAs derived from tRNAs that we called tRFs. These appear to have a variety of functions related to the regulation of gene expression. Long noncoding RNAs are also incredibly potent and diverse, with my lab currently focused on four out of the tens of thousands that are encoded in our genome. The ones we have focused on, APTR, H19, MUNC and DRAIC, have very strong biological effects on gene expression, differentiation or cancer progression, and there are thousands more sitting out there. So I feel like three beginning Assistant Professors rolled
into one, with three lifetimes worth of research ahead of me.

What advice would you give young students interested in biology?

Research in biology is among the most exciting, creative things I have encountered. It gives one a chance to do something important, something that can solve some of the biggest mysteries in our life while also perhaps improving human health. It is a wonderful time to get into research in biology…however, do not get into this career unless you feel passionate about research. This is not a career path for the faint-of-heart or for the thin-skinned. At every moment you will encounter critics who will nay-say your ideas, experiments will fail for the most trivial reasons, and even after you have managed to cobble together a set of experiments, the results may not be interesting enough to cause a stir. But you have to still remain excited about the questions you are asking to wake up the next day and jump in the fray once again. Those beautiful biographies that you read about scientists making brilliant discoveries and then being feted all over the world are more the exception than the rule. You have to be driven by your own curiosity, your own motivation to understand something, to discover something, come what may. This is a common thread in almost all creative areas of human endeavor, be it writing poetry or painting a picture. You should pursue it as a career only if you are remarkably passionate about your love for the process.

Would you choose this career path again if you were given the chance?

Absolutely! Despite all the complaints scientists are fond of reciting (poor grant funding, unhelpful administration, lab personnel not living up to their expectations, that ‘damned reviewer
number three’), most of my colleagues would not exchange this career for another. This is the real secret about
those of us who persist in academic research in biology. Many of us will still be dreaming of doing it even if our labs
are shut down and we are evicted from our offices.

Are you glad you chose this career?

I am ridiculously happy with my choice of career. I like being at the interface of medicine and biology, love the process
of teasing out a few biological truths, and am very happy to go to battle for funds or for acceptance of papers. I like
the give and take of science and the dialogue between like-minded people. I am incredibly fortunate to be born at this
junction of history where someone is willing to pay me so that I can discover something interesting or useful. My
parents were not so privileged because of their own particular circumstances, and centuries back humankind was so befuddled by superstitions, hunger and disease that no one from moderate means could imagine this career of
investigating life itself.

How has becoming department chair changed your view of science,
funding, etc?

My view of science funding has not changed at all. I came to run a lab in the early nineties when the level of science funding was as low as now. So I felt then and still feel that we can do better as a nation in funding more science. This democratic funding of science by national governments has been a game-changer, a very far cry from the sporadic efforts at research carried out by wealthy men in a few rich countries in the centuries before 1900. We have succeeded in bringing people from all corners of the world into the fold of researchers, and that remarkable infusion of talent is a very good thing for science.

My views about administration have changed for the better. As a professor it was easy to dismiss the higher administration as a bunch of know-nothings who were really looking after their own privileges. The view is slightly different from where I stand now at the interface of faculty and the higher administration. I realize now that most of the people in the Dean’s office or the University President’s office are making the best of some very hard choices. There is not enough money to support research in all the areas in which the faculty would like investment. The decrease of national funding for science is putting the higher administration at most universities and research institutions in an incredibly tough position: they have to balance the budget and cannot keep on supporting research that is not funded by external agencies.

What do you look for when hiring faculty into your department?

High quality publications matter, but not in the way some applicants worry. A paper in Nature, Science or Cell is not essential to get an interview. Instead, our search committees look for evidence of success as a leader of a project in different environments (e.g. the PhD and postdoc labs) — a few first-author publications that push a field forward in journals of reasonable reputation and outstanding letters of recommendation from multiple mentors. We are looking for applicants who can develop a good project and successfully compete for external grants once they become independent. The area of research is very important: some committees look to add hot new areas of research to a department’s current portfolio, others add to the current strengths to build a critical mass in the area, and yet others focus on match with institutional strategic plans. After these semi-objective screens, there are still 10–20 applicants who are comparable with each other and of interest to the department. This is when slight differences in letters of recommendation (or phone conversations with referees) and diversity requirements become important for determining a slightly subjective list of interviewees. At the interviews, the personality of the applicant matters significantly — is s/he a good speaker, intelligent, interactive, excited about the work and a potentially good colleague? Can s/he defend his/ her ideas well? How does the applicant deal with new suggestions? These are all the same considerations as when interviewing for any job that requires high cognitive skills.

How do you see the future of academic research changing?

Academic research in biology was lucky before the 1980s in that the common man and the legislators did not question
the value of investing in research. Once the era of ‘shrink the government’ began, research has been among the easier things to cut. Cuts in research funding do not affect as large a portion of the voters and the public discussion never comes round to the damage inflicted from missed opportunities. Science is not the only area that suffers: similar arguments are made about government support of education or of public infrastructure. I would like to believe that the realization will eventually sink in that government does some things remarkably well, like funding the basic research that is the foundation of future innovation. As an immigrant to the USA, I have great faith that this country
will eventually do the right thing. So I think that academic research will have at least some of its governmental funding restored, but I cannot estimate when this will happen.

So what has to change in the mean time? We have to go where the funding is. For better or worse, there is a current emphasis on translational research and on collaborative research by the funding agencies. We have no choice in academia but to move where the funding agencies want us to move, though we should bear in mind that NIH still supports a significant amount of investigator-initiated basic science research. Can private funds fill the void left by the retreat of government funding? Most private funds invested in blue skies research are small compared to government funds and are not distributed democratically. A few select institutions or laboratories may be able to fill some of the gap with philanthropic funds or with money from elite private institutions like the Howard Hughes Medical Institute, but the incredibly successful, highly democratic, all-embracing academic research in the USA that is the envy of the world can only be sustained by a restoration of public funding. Otherwise the academic research enterprise will continue to shrink to reach the levels before World War II, when the government was not a major funder of biological research. In those days the few important discoveries that were made were made at institutions like The Rockefeller University or Columbia University or Johns Hopkins, because they had access to rich donors. The advent of NIH funding changed that picture and led to all the miracles in
biological research and medicine that we benefit from today.

What’s the best advice you have been given in your career?

Ramzi Cotran, Chair of Pathology at Brigham and Women’s Hospital: “There is always a choice, the high road or the low road, when you encounter a problem at work. Always, always, take the high road.” Department of Biochemistry and Molecular Genetics, University of Virginia Medical School, Charlottesville, VA, USA.
E-mail: ad8q@virginia.edu

Current Biology 25, R1107-R1125, December 7, 2015