After completing school education in India, Mukherjee studied biology at Stanford University, obtained a D.Phil. from University of Oxford as a Rhodes scholar, and an M.D. from Harvard University. He joined the faculty of medicine at the Columbia University Medical Center in New York City in 2009. As of 2018, he is an Associate Professor of Medicine in the Division of Hematology and Oncology.
Featured in the Time 100 list of most influential people, Mukherjee writes for TheNew Yorker and is a columnist in TheNew York Times. He is described as part of a select group of doctor-writers (such as Oliver Sacks and Atul Gawande) who have "transformed the public discourse on human health", and allowed a generation of readers a rare and intimate glimpse into the life of science and medicine. His research concerns the physiology of cancer cells, immunological therapy for blood cancers, and the discovery of bone- and cartilage-forming stem cells in the vertebrate skeleton.
Siddhartha Mukherjee was born to a Bengali family in New Delhi, India. His father, Sibeswar Mukherjee, was an executive with Mitsubishi, and his mother Chandana Mukherjee, was a former schoolteacher from Calcutta (now Kolkata). He attended St. Columba's School in Delhi, where he won the school's highest award, the 'Sword of Honour', in 1989. As a biology major at Stanford University, he worked in Nobel Laureate Paul Berg's laboratory, defining cellular genes that change the behaviours of cancer cells. He earned membership in Phi Beta Kappa in 1992, and completed his Bachelor of Science (B.S.) degree in 1993.
Mukherjee is a trained haematologist and oncologist whose research focuses on the links between normal stem cells and cancer cells. Through his findings, he had shown the roles of cells in cancer therapy. He has been investigating the microenvironment ("niche") of stem cells, particularly on blood-forming stem cells (called haematopoietic stem cells ). Blood-forming stem cells are present in the bone marrow in very specific microenvironments. Osteoblasts, cells that form bone, are one of the principal components this environment. These cells regulate the process of blood cell formation and development by providing them with signals to divide, remain quiescent, or maintain their stem cell properties. Distortion in the development of these cells results in severe blood cancers, such as myelodysplastic syndrome and leukemia. Mukherjee's research has been recognised through many grants from the National Institutes of Health and from private foundations.
Mukherjee's team is also known for defining and characterizing skeletal stem/progenitor cells (also called osteochondroreticular or OCR cells). In 2015, they prospectively identified these progenitor cells from bone, and showed, using lineage tracing, that these cells can give rise to bone, cartilage, and reticular cells (hence the term "OCR" cells). They established that these cells form a part of the adult skeleton in vertebrates, and that they maintain and repair the skeleton.
OCR cells are among the newest progenitor cells to be defined in vertebrates. The work generated wide interest and was described in prominent journals as a major breakthrough for understanding biology and for understanding diseases such as osteoporosis and osteoarthritis. Mukherjee's team have shown that OCR cells can be transplanted into animals, and they can regenerate cartilage and bone after fractures. With Daniel L. Worthley's team at the University of Adelaide and South Australian Health and Medical Research Institute they have been working on the translational cell-based research on osteoarthritis and cancer.
Metabolic therapies for cancer
Mukherjee's lab has also been investigating the interaction between cancer genetics and the microenvironment, including the metabolic environment. It has been well established that metabolism in cancer is fundamentally altered, Mukherjee's team has found the role of a high-fat, adequate-protein, low-carbohydrate diet (ketogenic diet) in cancer therapy. They showed that ketogenic diet suppressed insulin production in the body, and this in turn enhances pharmaceutical inhibition of PIK3CA, a gene which is mutated and commonly overactive in cancers.
Immune therapies for acute leukemia
Mukherjee's lab, with the help of PureTech Health plc, has been investigating chimeric antigen receptor redirected T cells (CAR-T) therapy in a joint venture called Vor BioPharma since 2016. They have combined CAR-T therapies with genetically modified hematopoietic stem cells to specifically target malignant hematopoietic lineages, while transplanted stem cells replenish the lineage but remain antigenically concealed. This technology has been developed so that, in addition to B cell malignancies, other lineage specific cancers could be targeted. This provides an important new approach to managing acute myeloid leukemia.
Mukherjee's 2016 book The Gene: An Intimate History provides a history of genetic research, but also delves into the personal genetic history of the author's family, including mental illness. The book discusses the power of genetics in determining people's health and attributes, but it also has a cautionary tone to not let genetic predispositions define fate, a mentality that led to the rise of eugenics in history and something he thinks lacks the nuance required to understand something as complex as human beings. The Gene was shortlisted for the Royal Society Insight Investment Science Book Prize 2016, "the Nobel prize of science writing". The book was also the recipient of the 2017 Phi Beta Kappa Society Book Award in Science.
Chance events—injuries, infections, infatuations; the haunting trill of that particular nocturne—impinge on one twin and not on the other. Genes are turned on and off in response to these events, as epigenetic marks are gradually layered above genes, etching the genome with its own scars, calluses, and freckles.
The article, an excerpt from the chapter "The First Derivative of Identity" of his book The Gene: An Intimate History, was critiqued by geneticists such as Mark Ptashne, at the Memorial Sloan Kettering Cancer Center, and John Greally, at the Albert Einstein College of Medicine, because of over emphasis on histone modification and DNA methylation, while overlooking other important factors. They commented that these two processes have only minor influences in overall gene function. Steven Henikoff, at the Fred Hutchinson Cancer Research Center, opined that, "Mukherjee seemed not to realize that transcription factors occupy the top of the hierarchy of epigenetic information," and said, "histone modifications at most act as cogs in the machinery." It is now generally believed that histone modification and DNA methylations are major factors of epigenetic functions, aging and certain diseases, and with an ability to influence transcription factors. However, they contribute little to development. In response, Mukherjee did admit that omission of transcription factors "was an error" on his part.
Mukherjee also wrongly stated that "classical Darwinian evolution is that genes do not retain an organism's experiences in a permanently heritable manner... Darwin discredited that model [of Lamarck]." But Darwin had no idea of the gene—the concept of which was established only in the 20th century. Science writer Razib Khan noted this erroneous conception, and explained that "Darwin worked in the pre-genetic era... he himself was quite open to Lamarckianism in some cases."
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