R.S.K. Chaganti

Geneticist Raju Chaganti translated his early training in plant genetics to work in the developing field of human cytogenetics, which in turn led to his founding of Cancer Genetics, Inc. Since then, Dr. Chaganti’s research has helped to further the understanding of genomic instability in cancer cells.

In 1956, after Raju Chaganti finished his master’s and was working as a research assistant in plant genetics at Andhra University , he came across a paper in Nature written by two Englishmen, Charles Ford and John Hamerton, showing that humans had 46 chromosomes. He was unaware that the number of human chromosomes had been previously unknown, and became fascinated by this discovery. It seemed like a new field was emerging, and Dr. Chaganti thought that someday he should look into it. Being a part of a family of physicians, they received many medical journals at their home, including British titles like The Lancet. In these, he saw a set of papers by Charles Ford, in which he showed that individuals with Down syndrome and Klinefelter syndrome had extra chromosomes. That sealed Dr. Chaganti’s interest in this new field.

In 1960, he was accepted for admission to graduate school at Harvard to study under the renown corn geneticist Paul Mangelsdorf and received the Ph.D. degree.  Outside of his graduate school studies, Dr. Chaganti closely followed the advances in the emerging field of human genetics, especially cytogenetics and the study of the chromosomal basis of abnormal human development.

After being offered a position at the Medical Research Council (MRC) labs at Harwell, outside of Oxford in England, Dr. Chaganti went to the Ford lab where he stayed four years, and was trained in human and mammalian cytogenetics. At the time, human cytogenetics was mainly clinically oriented and had little research basis, so that’s what he focused his energy working on, using his experience from experimental plant genetics.

When he finished his postdoctoral research with Dr. Ford in 1971, Dr. Chaganti traveled to New York City to take up a position with James German, a renowned pioneer in human genetics. He spent five years with Dr. German, working on what were then called the chromosome breakage syndromes, such as Bloom syndrome, which predisposed individuals to cancer, and on sex-chromosome disorders in humans.

At the end of his five years in the German lab, Dr. Chaganti was brought in to the Department of Pathology at Memorial Sloan-Kettering (MSK) to develop a diagnostic cytogenetics laboratory with only one technician. At the time, there was only one chromosomal marker in cancer to track, the Philadelphia chromosome, which was a diagnostic marker of chronic myelogenous leukemia (CML), and this was the initial focus of the new lab. Dr. Chaganti wanted to start a research program to discover more chromosome markers. He did so along with several other researchers from around the world, and published a great deal of groundbreaking work on the chromosomal basis of cancer development. They were helping to define the newly emerging field of cancer genetics.

Dr. Chaganti had his clinical appointment at Memorial Hospital and an appointment at Sloan-Kettering Institute doing basic science research, both of which he continues to hold in the Department of Medicine and the Cell Biology Program. Earlier, as a member of the Department of Pathology, he had a great deal of exposure to cancer pathology. Back in the late 1970s and 1980s, Dr. Chaganti was looking for a cancer type to study using genetic techniques and gravitated towards two types of cancer: lymphoid neoplasms and germ cell tumors. Dr. Chaganti chose these because he knew they were cancers arising in developmental lineages. It seemed to him that these would be cancers for which he could ask some basic questions.

That proved to be very rewarding work for Dr. Chaganti. Just as he was beginning his work studying lymphomas, the MYC translocation in Burkitt lymphoma was discovered. Dr. Chaganti’s group were eventually able to identify many new translocations and identify their genes in other lymphomas. The most significant of the genes discovered was BCL6 which is now known to play a key role in normal B-cell development and its transformation to diffuse large B-cell lymphoma, an aggressive form of this lymphoid malignancy.

By the mid-1990s, the emphasis of the lab switched from lymphoid tumors to germ cell tumors, the genetics of which they had been studying for a number of years by then, in collaboration with George Bosl, current Chairman of Medicine at Memorial Sloan-Kettering. They were questioning how these cells retain their memory of pluripotency (the ability of a cell to develop into any cell lineage), as well as how they reactivate it in the tumors. At the time, there weren’t many possible explanations for this.

But then, in the 1990s, high-throughput gene expression profiling technology using microarrays was developed, which allowed the expression pattern of all the genes in the genome to be scanned in one experiment. Dr. Chaganti thought he could use this technology to see how lineages were forming in germ cell tumors based on changes in gene-expression patterns. Today, it is known that there are three kinds of pluripotent cells: embryonic stem cells, induced pluripotent cells, and embryonal carcinoma cells. Embryonal carcinoma, deriving from germ cell tumors, is their system of study. With the new data that they acquired, Dr. Chaganti and his team had some good clues as to how lineages were put together. However, the data was so vast that the traditional methods of data analysis would not work satisfactorily. They needed to reduce this data into hypotheses that could be tested. Dr. Chaganti’s interest is transcription factors, specifically how to reverse engineer transcription factor networks from gene-expression profiling data. This requires advanced computational biology techniques, which were beyond his knowledge or capability.

In 2006, Dr. Chaganti began working with Dr. Califano, a leading expert in the field of Systems Biology and together they developed an exciting program trying to reconstruct transcriptional networks that regulate pluripotency and lineage development in the context of a cancer phenotype. This has led them towards stem cell biology, which has become one of the main focuses of his lab at this time. They have recently discovered some new transcription factor modules that regulate pluripotency.

Amongst all of the research he was engaging himself in, Dr. Chaganti, along with several business partners, founded Cancer Genetics, Inc. in Massachusetts (Cambridge and later at Milford) in 1999. At that time, the company was comprised of a Clinical Diagnostics Division that focused on cytogenetic and molecular cytogenetic assays and a Research and Development Division that initiated the development of the current DNA-FISH Probe portfolio. The Company sold the Clinical Diagnostics Division in 2004, and moved to New Jersey in 2005. In 2006, the Clinical Diagnostic Division was successfully re-launched with a newly established Molecular Genetics Subdivision. CGI’s scientific advisory board, which works closely with Dr. Chaganti, currently includes leading specialists in clinical cytogenetics, as well as significant thought leaders capable of driving adoption in the tri-state area.

Dr. Chaganti is an internationally recognized leader in cancer cytogenetics and molecular genetics, and holds several patents through Memorial Sloan Kettering Cancer Center as well as Cancer Genetics. He has witnessed a vast number of scientific breakthroughs and discoveries in the decades he has devoted to the field of science. He was an integral part of new methods of scientific investigations, including significant advances in both clinical and basic scientific research. Dr. Chaganti has served on the boards of many prestigious journals, and has received numerous honors throughout his career, including the Fellowship of the American Association for Advancement of Science and the Founding Fellowship of the American College of Medical Genetics.