Professor of Genetics,
Executive Director of Yale Center for Genome Analysis,
Director, Yale Center of Proteomics,
Principal Investigator, Yale/NIH Centers of Mendelian Genomics, Yale University School of Medicine, Connecticut, USA
Dr. Mane’s work involves the discovery of genes and genetic changes responsible for various human diseases, and to develop appropriate genomic technologies necessary to make these discoveries.
Coming from a low-income family of sugar-cane farmers in a small village called Rahimatpur near Satara, Dr. Shrikant Mane has established himself as a leading geneticist in USA. He founded Yale Center of Genome Analysis, one of the most renowned and scientifically accomplished genome centers in the world, that has attracted more than $300 million funding to carry out genomic research at Yale.
Dr. Shrikant Mane did his PhD from Tata Cancer Institute, Mumbai and went to USA as a post-doctorate fellow at Johns Hopkins School of Medicine. After the fellowship, he was offered a junior faculty (instructor) position at the Johns Hopkins School of Medicine. But in those days, federal funding for research was getting scarce and he ended up moving to a biotechnology company. He worked there for four years and received three patents for growing bone marrow stem cells outside the human body and development of a replacement of blood vessel using ePTFE (Teflon) material.
However, he was not content with the industrial environment as there was a lack of freedom to pursue his own research ideas. He decided to pursue research and accepted an offer from Yale University, Connecticut. At Yale, he was hired to establish a then cutting-edge microarray technology to support genetic research. Looking back, he feels that Yale provided him with the best possible support and they also believed in his abilities. He had total freedom and full financial support. He worked very hard and immersed himself completely in research. His group published the first article in 2005 discovering a gene for age related macular degeneration. This publication received an instant recognition as the landmark study that started the beginning of current genomic and precision medicine era. Later that year,he also received a prestigious and extremely competitive $7.5 million grant from the National Institute of Health to establish a national Center to study the genetics of neuroscience.
To understand the research work of Dr. Mane, let us understand what is ‘Genomics’ and what its role in ‘Precision Medicine’ is. In his own words, as Dr. Mane explains, “Genomics is the study of genes and how they function. We all know that the genes control our development and bodily functions. Genes are made of DNA and are the basic physical and functional units of heredity. A complete set of DNA, including all of its genes is called a genome. Our genome contains approximately 20,500 genes and is passed by parents to their kids from generation to generation, which explains why children tend to look like their parents and have similar tendencies. Genes act as a set of instructions, directing our body to make all the proteins that control and perform all our bodily functions. The information in DNA/Genes is stored as a code made up of four different kinds of chemical bases. Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The less than 1% differences or variations in the DNA make each individual unique. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. The DNA sequence of a gene can be altered or mutated in a number of ways. Some of these genetic mutations result in faulty genes, causing it to alter the function of proteins leading to many human diseases. By ‘sequencing’ or ‘reading’ the human genome, we have opened a goldmine of valuable information about the faulty genes that give rise to certain diseases”.
Dr. Mane says, “The current medical practice is a “one size fits all” practice. It is identical to what doctors would hand over to essentially anyone with the same illness. That is because medicine as we know it today revolves around “standard care”, the best course of prevention or treatment for the general population. However, the same treatment may not work for everyone and the side effects of the medication vary from person to person depending on his specific genetic code. But slowly, we are now entering the new era of “Precision Medicine” that tailors medical care to individuals based on their genetic makeup. New innovations in genomics will allow us to more precisely predict, diagnose, and treat conditions in individual patients, instead of having to settle for the current one-size-fits-all approach. This is more useful in case of early diagnosis and treatment of the diseases like cancer, AIDS, diabetes, and cardiac diseases. For example, a person’s genomic information could indicate a higher than average risk of developing diabetes or particular form of cancer. Armed with this information, that person could make life style changes or take prescribed medication to better regulate the aspects of health and wellness, which will help counteract the genetic risks. This is where my research of Genomics comes into picture”.
After receiving the extremely competitive and prestigious grant from the National Institute of Health in 2005 to study the genomics of nervous system, Dr. Shrikant was interviewed by the Associated Press. His interview appeared in major newspapers in the US as well as around the world. Later in 2008, he was probably the first scientist to receive a $ 1.2 million grant to purchase Illumina Next Generation Sequencing (NGS) technology. His collaborative efforts were paid big time when Yale received more than $45 million funding through President Obama’s stimulus package. Yale also recognized Dr. Mane’s contribution by honoringhim with the task of founding the Yale Center for Genome Analysis with generous $10 million funding from the Provost.
Dr. Shrikant Mane reached another mile stone in 2009 when his group published the article describing the development of whole exome sequencing technique that is now being used all over the world for both research and clinical applications. This was also the first report describing the use of powerful NGS technology for the clinical diagnostic purpose. These studies strengthened the precision medicine approaches he had initiated in 2005. The precision medicine is the future practice that will completely revolutionize the way medicine is practiced today. President Obama announced the precision medicine initiation with more than $250 million funding and empowered Dr. Mane’s mentor and ex- supervisor Richard Lifton to implement it in the United States. It is already being practiced for cancer and few other diseases.
In 2011, Yale Center for Genome Analysis thatDr. Mane founded was awarded another prestigious $11.5 million grant by NIH to study Rare/Mendelian Disorders. The studies conducted through this funding identified genetic factors for several human disorders including, congenital heart diseases, skin disorders, abnormal brain development, kidney and immunological disorders. These studies led to the publications of more than 25 articles in prestigious journals including Science, Nature, Cell, New England Journal of Medicine and Nature genetics. This success led to another successful award of $12 million in 2015 by National Institute of Health(NIH) to continue his studies with rare disease. The Genome Center founded by Dr. Mane has emerged as one of the most scientifically productive genome centers in the world and has attracted more than $300 million funding to carry out genomic research at Yale.
Dr. Shrikant feels, “I suppose my leadership at Yale has enabled me to establish a world-renowned genome center that has discovered genes responsible for numerous human diseases, attracted millions of dollars of funding and achieved worldwide recognition for both myself and my university.”
Dr. Mane says from an early age of 8, he wanted to be a scientist and go to America to do the research. That is why even if his parents wanted him to be a medical doctor, he kind of rebelled and went for pure science and did PhD and later postdoctoral research in USA. He says, “My parents were not very pleased with my choice of my professional career. They very much wanted me to become a medical doctor. Despite feeling the tremendous pressure and burden of their expectations, I rebelled and decided to follow my dream of becoming a scientist. They continued to be very displeased with me for most of my early career until I received a $7.5 million grant from the National Institute of Health in 2005 to study the genomics of nervous system. .I value this achievement most in my life because then on, my parents realized the importance of work I was doing and were proud of my achievements”.
Childhood and Schooling:
Shrikant was born in March 1957 in a small village called Rahimatpur near Satara in India. Despite his family’s humble beginnings, Dr. Shrikant Mane’s parents were dedicated to making things better for their children. His family had a strong belief in the importance and power of education. His grandfather was a principal of a primary school and used to teach him arithmetic in the evenings. His father was a dedicated and accomplished high school math teacher who not only taught during the day, but also participated in his farming duties before and after school hours. He actively promoted education for girls, poor and minority students in particular during a time and place when addressing the needs of these vulnerable groups was not common. Shrikant’s father made sure that most of the girls in their extended family received at least a bachelor’s degree. Both of Dr. Shrikant’s uncles were educated abroad and set a good example for him. His sisterSanjivani completed her master’s degree in languagesand herself became a driven and caring principal of a girls’ high school in another town. HisbrotherSudhir received a civil engineering degree and has now risen to a high position in the agriculture department of state of Maharashtra. Shrikant’s mother Shankuntalawas a house wife who helped his father with the farming and of course looked after her kids. Shrikant’s both parents were very hardworking, honest and principle-minded. Above all, they focused on their children’s education and wellbeing by sacrificing almost everything in their own lives to save money for kids’ education. They also instilled in them good values such as respect for teachers, honesty, and the importance of hard work over material wealth. His father was very active in the Boy’s Scout’s equivalent in India and earned medals for the school at the state level in various activities. He also taught swimming and math to many interested children during summer vacation. In addition to academics, his parents exposed Shrikant to extracurricular activities such as sports, drama acting and exercise- they taught the very important lesson of not being ashamed to work hard and play hard. On weekends and summer holidays, Shrikant used to assist his parents in various farm activities.
Dr. Shrikant says, “My childhood was very happy since I was the first grandchild in a large family of 25 people and thus, I received a lot of attention. I was very witty and was very inquisitive. Due to my curiosity, I used to ask lots of questions almost about everything. Since I was the eldest in the family my parents and close family members and also some townsfolk used to call me “Dada” which means “elder brother” which they still do. As a child, I was very mischievous and used to get into many fights with other school children. Hence, I got another nickname- ‘Bhim” (From Mahabharata). Thankfully, as I grew up I lost my combative nature and actually became rather shy and quiet”.
“My uncles tell me that even at the age of 10, I somehow knew that I would be doing research and one day be in the United States. Looking back at my life I think this trajectory/road opened for me automatically, as if it was my destiny”.
“I attended primary school and high school in Rahimatpur. Every morning I used to go the teacher’s room and bow to each and every one of them. The teachers were fond of me because I was an obedient and diligent student. Thanks to the many schoolyard fights I was involved in,I received lots of scolding and beating from the teachers as well as from my parents. One of my earliest memories of primary school involves collecting cow-dug every Thursday morning, and spreading it on the classroom floors to smoothen them”.
“My parents wanted my siblings and me to excel in academia and more importantly learn life-long good habits. Since I was the eldest in the family, they particularly focused on my studies and behavior. They specifically instructed my teachers to be strict with me and to not hesitate to punish me for my inappropriate behavior. Due to all this attention and discipline, around the age of 7, I turned into a very quiet and shy person. I was respectfully frightened of my parents. Sadly, this came at a price, as fear of my parents caused me to lose the opportunity to become close to them”.
“I attended AdarshHigh School in Rahimatpur. This was a brand new high school and I was in the first batch of 8th grade students. The school had no funds and hence no facilities. Our first class was conducted in an abandoned chicken wire cage. People who had large houses offered rooms to conduct classes. Despite poor conditions, I was very content as a student since teachers were loving and dedicated. The school had a hard time finding a good English teacher in particular – the one the school hired had a history background and was making efforts to teach us English, but it was not adequate. When my father realized this, he requested one of the retired English teachers in next town to teach me three days a week. My love of knowledge and school, combined with my natural ability were recognized and special attention was paid towards my education. I loved science and math especially and excelled in my studies as well as sports – I was a captain of the school cricket team. Despite my talent in sport, my parents did not provide much encouragement since they wanted me to focus on my studies instead. My father was our math teacher, and he was a very dedicated and good one. However, he was very strict and all students, including me, were afraid of him. At that time, fear was the mantra and catalyst that motivated students to learn. My father and most of the teachers utilized fear unapologetically to make sure students paid attention and behaved well”.
“I used to always stand first in the class and was therefore respected by my teachers.Yet, during my high school days, I was very quiet and inhibited from expressing myself since I was afraid of my father. I felt that he and other teachers were constantly watching me since they had lots of lofty expectations from me. To make things worse, I was honored in tenth grade with the title of the “ideal student” of the entire school. Despite receiving this accolade, I was not thrilled with this honor since it put even more pressure on me to never deviate from my father’s expectations. This childhood fear and pressure never truly left me, and I feel it robbed me of the spontaneity and fun of a childhood. Now looking back, I feel a good life is not one that exclusively focuses on studies and awards; it is equally (if not more) important to cherish the fun, the adventures, and more loving aspects of family and life”.
“My leadership qualities were evident during my school days. I was interested in sports, especially cricket. I convinced a few of my friends to form a team. However, we were poor and had no money to purchase an expensive cricket bat. I came up with the idea that we should collect donations from the wealthy town members. None of my friends believed in me. However, I went door to door and convinced several people to donate enough money to purchase all of the required cricket accessories. These efforts led to the formation of a formal cricket club in my town which conducted several matches with neighboring towns”.
Shrikant’s bachelor’s studies were completed at the Science College at Karad, affiliated with Shivaji University. Going to college was a big step for him, as he had to leave his small hometown behind and move to a large, metropolitan city. The first six months of college were thus difficult; he struggled being away from home for the first time and found it challenging to adjust to all-English lectures. However, he recovered after a few months mostly due to the company of good friends.
He was an outstanding student in college. He was also a great cricket player and was the captain of the college team. During his third year of college, he came in close contact with one of his Zoology ProfessorsProfessor RameshChandak who was an exceptionally good genetics teacher. He recognized Shrikant’s potential and introduced him to the research world and gave him Scientific American and other journals to read. He was mainly responsible for developing Shrikant’s interest in genetic research. Dr. Shrikant says, “I will never forget his contribution to what I am today and have kept in touch with him over the past 40 years”. Shrikant graduated from the Shivaji University with distinction and ranked in the first three in the university.
Shrikant wanted to do his masters at the same university. But one of the professors, who later became the vice chancellor of the university, suggested that he should join the Institute of Science in Mumbai instead. With his recommendation Shrikant was admitted at the Mumbai University to study animal physiology at the well-known institute of Science. He also was able to secure a prestigious Daxina fellowship for the master’s program. This fellowship offered a generous allowance that covered all of his expenses. He secured a master’s degree with distinction.
It was Shrikant’s childhood dream to specialize in cancer research and become a biomedical scientist in the United States. He applied for PHDprograms at the Mumbai University and at the Tata Cancer Research Institute. While he was waiting to know the outcome of his PHD applications, he worked at the Khalsa College in Matunga as a lecturer in genetics and cytology. He quit this job after six months when he secured an admission for PhD program at the Tata Cancer Institute. Due to his position as one of the university’s top students and his keen interest in research, he was selected by the director of the instituteDr. Deo as his protégée.
Dr. Shrikant says, “I think this was my true lucky break since my PhD advisor was an incredibly talented and devoted scientist. Importantly he had a very positive attitude and provided lots of encouragement and support to me during my PhD work. During my first year at Tata I was very fortunate to come in close contact with Dr George Kohler, who went on to win a Nobel Prize for developing monoclonal antibodies. He was a PhD student when he visited my institute. My PhD advisor asked me to pay special attention to Dr Kohler; the two of us spent two weeks together during which he taught me the technique of raising monoclonal antibodies. I was very impressed with Dr Koehler’s simplicity and his passion for science. From Dr. Kohler, I learned the very important lesson of being humble and true to science”.
“During the course of my PhD, I discovered a growth factor that was later identified as the Transforming Growth Factor (TGF). TGF plays a very critical role during development and several physiological processes in human body. My research work was so impressive that I was honored to present an annual institutional seminar even though I was still only a first year graduate student”.
Dr. Shrikant left India in 1985 immediately after receiving a Ph.D. At that time, it was very difficult to get a research scientist position in India. Moreover, funding was not adequate for the type of research he wanted to do. Besides, it was his lifelong dream to go to USA to do the research. He got an opportunity to do a post-doctoral fellowship at one of the best universities-Johns Hopkins- in the world and he felt like the destiny was inviting him to USA.
However, Dr. Shrikant’s life journey was not always smooth. He did face setbacks a few times. He said, “I suffered a major depression attack when I was in the last year of college. These attacks continued on and off for the next 20 years turning me into a helpless person on occasions. Medication was not an option since they did not work for me. I studied psychology and meditated regularly to cope up with it. Today, with the help of meditation, I am completely depression free”.
Another struggle was for funding of his research in USA. He said, “Due to funding challenges I kept losing job after job for few years. In order to make a living I was separated from my family for a long period of time. I missed my family and struggled with loneliness. Instead of getting depressed, I focused on my work with more determination and passion to make an impact on human life. During these times, I was touched by the compassion and support from many of my American and Indian friends”.
Later while Dr. Shrikant was establishing a genome center at Yale in 2009, his both parents fell seriously ill and needed frequent hospitalization. For a period of four years, Dr. Shrikant ended up spending 3 to 4 months every year in India taking care of them. He had a demanding and high-profile job at Yale. Besides, taking care of two sick people was physically and mentally exhausting for him. He used to spend his day time taking care of his parents and did his work and attended conference calls during night. He recalls, “Several Indian doctors and friends rushed to help me. My superiors and colleagues at Yale were also supportive and understanding. Many of my doctor colleagues went out of way to evaluate my parent’s health and suggested new treatment options.Even though it was extremely challenging for me to take care of my parents while maintaining my high stressjob in USA, I was and am very happy and thankful to God for giving me the opportunity to take care of my parents”.
Dr. Shrikant feels grateful towards his parents, grandfather and his teachers who not only gave him the immense knowledge but also helped him develop his character and attitude. He wishes to thank his wife, children and uncle who believed in his abilities and provided constant encouragement, especially during his down periods. He says, “My lovely two daughters have provided me the strong incentive for not succumbing to the depression and made me focus on my work”.
Dr. Shrikant is still in constant contact with his roots. In his own words- “I am still in contact with all my relatives, friends and teachers from my home town. I still enjoy being in my home town and spend time at my father’s farms. It makes me feel at home. During my trips to India I make efforts to meet the people and teachers who believed in me and provided inspiration. In the past few years I have been visiting India several times a year to give seminars and share my knowledge. The incidence of some rare diseases is very high in India due to marriages between close relatives. I am trying to develop collaborations with Indian scientists to identify causes of these diseases. I am also trying to develop several collaborations with the prominent hospitals to bring them up to date with the genomics and its clinical applications”.
“Since 2010, I have been trying to transfer exome sequencing technology to India. I met with DrPratap Reddy, Apollo Hospital several times to make this happen. I also interact with the Indian Council of Medical Research, prominent geneticists and several hospitals to share my experience and offer to provide training to clinical geneticists and scientists. I participate in several international conferences in India to give seminars and share knowledge. After I retire I am planning to volunteer for teaching and improving health practices. I also offer guidance to young students who are trying to come to USA for further studies”.
Dr. Shrikant is very optimistic about his outlook towards India. “Indian economy is growing at a very high rate now. I think India has a great future since significant resources are now available to do the research in the areas that matter the most. Theinfrastructure is being built and most importantly public attitude towards corruption is changing. India is going to be one of the superpower very soon due to these changes. The world has always recognized the spiritual leadership of India. Recent research effort is providing more insights into meditation, yoga and other spiritual practices. Indian doctors, scientists and entrepreneurs shine in the western countries due to the opportunities and environment. India’s environment is changing and more opportunities are being created due to large amount of investments. Because of these activities I am confident that India will provide a scientific/technological and spiritual leadership to the world.”
Advice to Youth:
Dr. Shrikant thinks, “Passion, dedication and perseverance were the key for my success. Be patient, do not get discouraged by setbacks since everything goes in cycles- good days follow the bad days. Proper attitude and positive thinking surely result into a big success”.
His advice to youth is, “Don’t give up. Persevere! Does not matter how small you begin and how often you feel knocked down, dust off, stand up, believe in yourself and move on!”
Dr. Shrikant Mane is married to Suneeti who was also a doctoral student with him at Institute of Science and at Tata Cancer Research Institute. He says it is a funny story how he met his life partner.
“It’s a funny story. After graduating from an out of town university, I attended the University of Bombay for my Master’s degree. It turned out that the students from Bombay Uni. did not think much of us outsiders!This fact became very obvious when one day after one of my classes at the Institute of Science; as I a class at Institute of Science as I was walking out of the building I heard someone call my name. I looked back and found a girl trying to catch up with me. She asked me if I just took theadmission for MSc and asked me what my score was. She was surprised to see me in that class. When I told her my score she was not convinced and atfirst asked me which university I got my education from. Then when she came to know that I received these good grades from a university other than University of Bombay, she just said, ‘Oh that University!’ and left!
Obviously, there was no reason for her to linger. We were classmates for two years and I believe she did not think much of me. As luck would have it, we met again in the same graduate school as Ph. D students. Thankfully she changed her opinion of me when she heard me give a talk about my research. She was also present at this seminar. However, after witnessing my seminar performance she eventually changed her opinion. This led her to fall and fell in love with me.
Many years later, I found out that she had thought of me simply as the villager’s simple son and a small-town guy lacking in sophistication. Of course, according to her the two years doing Masters in Bombay University had significantly ‘improved’ me! Even today, she lovingly takes a stick in the hand to correct my English.
Dr. Shrikant and Dr. Suneeti are blessed with two daughters.
My elder daughter, Aparna received a law degree and now is working as a public defender in Arizona. My younger daughter, Aditee completed her Master’s in Business from University College London and is now working as an account manager in a private video technology company in London, UK. My wife completed her PhD at Tata Cancer Hospital and moved to US with me in 1985. She is currently working at Roche Pharmaceutical as a project leader.
Major achievements in life:
1) Published the first article after the completion of human genome project in 2005, which identified the gene for age-related macular degeneration. This article was published in Science as a cover article and is considered to be a landmark publication that marked/started the current genomic and precision medicine era.
2) Develop the exome sequencing technique using Roche/NimbleGen platform in 2009. This article was also the first to use exome/NGS for clinical diagnostic application. The exome sequencing I developed is now used worldwide for both research and clinical diagnostic purposes.
3) Attracted more than $45 million funding as a principle investigator and >$ 250 million as a collaborator on Center and individual research grants from National Institute of Health and other extramural agencies.
4) Founded a world class genome centerat Yale University (Yale Center for Genome Analysis: YCGA). As an executive director, I have led this genome centerto be one of the most scientifically prominent genome centers in the world. The YCGA has attracted more than $300 million in funding and has published more than 350 articles describing high profile discoveries for various diseases including cancers, psychiatric disorders, skin disease, cardiovascular diseases and developmental disorders in reputed journals including Science, Nature, Cell, and the New England Journal of Medicine and Nature Genetics.
5) One of the principle investigators of the highly regarded Yale/NHGRI Centers for Mendelian Genomics. This Center is funded through a $22 million grant from the National Human Genome Research Institute.
6) Have authored more than 140 peer reviewed articles describing the development of genomic technologies and identification of disease-causing genes in several human diseases. More than 20 of these articles are published in high profile journal such as Science, Nature, Cell, New England Journal of Medicine and Nature Genetics. These ground-breaking discoveries are making a huge impact on the lives of millions of humans suffering from various diseases including various cancers, psychiatric disorders, eye diseases, skin and liver disorders.
7) Established Yale/NIH Neuroscience Genomic Consortium Center in 2005 funded by a $6.5 million grant from NIH (PI: S. Mane)
Special certifications, Honors:
Daxina Fellowship for Master’s Degree
Fellow of American Association for the Advancement of Science
Invited Key Note speaker for several international conferences
Interviewed by Associated press in 2005 after receiving a prestigious grant to study neuroscience
Professorship at one of the most renowned universities (Yale) in the world