Served as Ph.D. examiners for University of Pune, Mumbai and Delhi
Reviewer for journals such as Endocrinology, Biology of Reproduction, J. Molecular Endocrinology, Molecular and Cellular Endocrinology. Nature Scientific Reports and Tumor Biology, Member Review Board E‑Life
Member of SERB task force on Animal sciences, SUPRA, POWER and IRPHA projects
Significant scientific contributions of Prof. Dighe, MRDG, IISc
Prof. Dighe has been associated with the Indian Institute of Science, first as a Ph.D. student from 1975 to 1981 and then as a Scientist and faculty from 1985 to present and is currently a professor in the Institute. He also served as the Chairman of the Department of Molecular Reproduction, Development and Genetics of the Institute from 2005 to 2010.
Prof. Dighe established a frontline line research group active in the fields of Molecular Endocrinology,
Reproductive Biology, Biotechnology, Cancer immunotherapy, Antibody engineering and Therapeutic protein expression. His scientific contributions have been widely recognized as indicated by the fellowships of the scientific academies, the National Academy of Sciences, the Indian Academy of Sciences and the Indian National Science Academy. He was also awarded the prestigious J.C. Bose National fellowship and the Alumni award for excellence in research in Science by the Indian Institute of Science for the year 2016. Earlier, he was awarded the Rockefeller Foundation the career development award in biotechnology. Recently, the University François-Rabelais of Tours, France awarded him the visiting Professorship. He has published several papers in the peer-reviewed journals that have been extensively cited.
The research activities of his laboratory are a combination of the basic and translational research. Earlier studies from the laboratory concentrated on interactions between the glycoprotein hormones, the hormones that regulate reproduction (gonadotropins) and overall physiology (TSH) and these studies provided molecular insights into hormone receptor interactions and activation of receptors. The interesting feature of these research activities was the imaginative usage of antibodies- polyclonal, monoclonal and recombinant- to understand the molecular details of hormone action and have led to elucidation of the receptor binding domains of the hormones. Similarly, the antibodies against different fragments of glycoprotein hormone receptors helped in identifying the domains of receptors involved in hormone binding. These studies also revealed the molecular details of receptor activation.
The antibodies against the hormones were also used to investigate the physiological roles of gonadotropins in regulating the male reproductive function. In a well-cited paper, Prof. Dighe’s group conclusively demonstrated the role of Follicle Stimulating Hormone (FSH) in adult
spermatogenesis ending a long-standing debate in the field of Reproductive Endocrinology. Recently, a new research program has been initiated to identify the genes responsible for human infertility. This project involves analysis of gene expression in the testicular germ cells of patients with arrested spermatogenesis using tools such as microarray analysis and bioinformatics. This project is expected to identify the gene(s) responsible for human infertility.
Biotechnology of Gonadotropins is another significant achievement of Prof. Dighe. These hormones are required for IVF programs and are quite difficult to express due to their complex structures and requirement for glycosylation during biosynthesis and yields of biologically active hormone are usually very low. For this purpose, the Pichia pastoris yeast expression system was established to produce the human hormones, particularly the gonadotropins. Since the Pichia-expressed gonadotropins exhibited very low in vivo biological activity, which shown to be due to hypermannosylation of the proteins by the wild type Pichia, the glycosylation pathway was altered to produce the hormonal proteins with human like glycan moiety which led to expression of hormones that exhibited complete in vivo biological activities. This is a very significant biotechnological achievement and an important step for production of therapeutic human proteins, many of which are glycoproteins. It is now possible to produce large quantities of therapeutic proteins using the Pichia system.
Another important achievement is the production of recombinant human and bovine gonadotropins using the mammalian expression system and attempts are being made to develop clinical and veterinary preparations of these hormones.
The laboratory was also involved in developing novel approaches for vaccines for contraception in animals and also various diseases including cancer. The Dendritic cells play an important role in antigen presentation. Prof. Dighe’s laboratory characterized several recombinant antibodies or Single Chain Fragment Variables (ScFv) that can recognize the unique receptor, DEC205 present on the dendritic cells. Further a methodology was developed for combining an any antigen with these ScFvs allowing the delivery of the antigens directly to the dendritic cells. This results in sustained immune response to very small quantities of antigens and the strategy is very useful in mass immunization when the availability of antigen is limiting and sustained immune response for long periods is required. Right now, this strategy is being employed to develop a contraceptive vaccine strategy for stray animals. The same methodology can be used to deliver cancer antigens to the dendritic cells, thus creating an interesting strategy for therapeutic cancer vaccines.
The recent trend in the biological science is the development of therapeutic antibodies and several antibodies are in various phases for clinical trials for treatment of different cancers. For last few years, Prof. Dighe’s laboratory has been exploring the possibility of developing such therapeutic antibodies for treatment of cancers in which there is an upregulation of Notch signaling. It was demonstrated that inhibition of Notch signaling using antibodies- polyclonal, monoclonal and recombinant – capable of inhibiting Notch function can be an excellent tool for cancer therapy. The group has characterized a novel monoclonal antibody that specifically recognizes the “Gain ‑of-function” mutation in Notch1 responsible for T cell leukemia. This MAb has much higher affinity for the mutant Notch compared to the wild type Notch and thus has preferential effect on the cancer cells. The Notch antibodies were shown to be more effective for cancer. The group is also characterizing ScFvs against different Notch proteins and investigating their effects on ovarian cancer.
The laboratory of Prof. Dighe has made a major effort in understanding of gene expression in human testis and correlate to arrest of spermatogenesis that leads to infertility in human males. Several potential genes, whose expression was altered in the germ cells of infertile males have been identified
Indian Institute of Science
University of Bombay
University of Bombay
- P. P. Surya Kumari medal for the best paper in Endocrinology by the Indian Pharmacological Society 1985
- Career Development award by the Rockefeller Foundation, USA 1987
- Subhash Mukherjee oration award by the Endocrine Society of India 2008
- Fellow, National Academy of Sciences, India 2009
- Fellow, Indian Academy of Sciences 2010
- Fellow, Indian National Science Academy 2010
- J. C. Bose National Fellowship 2014
- Visiting Professorship, the University François-Rabelais of Tours, France 2016
- Alumni Award for excellence in Research for Science of the Indian Institute of Science for 2016
- INSA Senior Scientist 2019