Ram Sasisekharan

Ram Sasisekharan (born 1965 ) is an Indian-American researcher and bioengineer at the Massachusetts Institute of Technology (MIT). Best known for leading the international team that identified oversulfated chondroitin sulfate as a contaminant in the US heparin supply in 2007 and 2008, he had developed antibodies for dengue, yellow fever, Zika and SARS-CoV-2 infections.

Sasisekharan joined the MIT's faculty of biological engineering in 1996, became full professor in 2003, and Director of the Harvard–MIT Program in Health Sciences and Technology from 2008 to 2012. Since then, he is the Alfred H. Caspary Professor of Biological Engineering and Health Sciences and Technology at the MIT's Koch Institute for Integrative Cancer Research. He is also a principal investigator of the Infectious Diseases Interdisciplinary Research Group under the Singapore-MIT Alliance for Research and Technology.

Sasisekharan's research in glycomics and antibodies, with authorship of about 200 scientific papers, led him found six biotechnological companies for which he is a named inventor on 205 United States patent applications in 2023. His PhD research, supervised by Robert S. Langer, on cloning and sequencing of the enzyme, heparinase, led to the creation of his first biotechnological company, Momenta Pharmaceuticals, which was later acquired by Johnson & Johnson.

Background and personal life Sasisekharan was born in India in 1965. His father, V. Sasisekharan (Viswanathan Sasisekharan), is an Indian biophysicist whose research involves the structure of biomolecules including that of DNA. Sasisekharan's wife, Uma Narayanasami, is an oncologist certified in hematology and medical oncology practicing at Mass General Cancer Center at Emerson Hospital in Concord, Massachusetts. She has also collaborated in the fight against cancer and has had several publications focused on heparinase and its potential to limit tumor growth by releasing certain sugars from the surface cells of cancer. He earned his doctorate in 1992. He later described the problem by comparing his work with DNA sequencing: "Sequencing DNA is like walking through a ladder, but sequencing sugars is more like putting a puzzle together."

Early career Sasisekharan's PhD work, under the supervision of Langer, was one which most researchers avoided due to the difficulty and risk. It involved characterizing and sequencing the components of heparinase, a critical enzyme that degrades or cuts up the sugars in the heparin family. From 2007 to 2008, the US Food and Drug Administration FDA approached Sasisekharan to use his glycan sequencing technology to identify the source of a contaminated batch of heparin. Weeks later, the Sasisekharan lab helped identify the contamination source as oversulfated chondroitin sulfate.

Sasisekharan joined the MIT faculty in 1996, received tenure in 2001, and advanced to full professor in 2003. From 2008 to 2012, Sasisekharan was the Edward Hood Taplin Professor of Health Sciences and Technology and Director of the Harvard-MIT Program in Health Sciences and Technology.

Research Protein sequencing Considered a pioneer of the emerging and essential field of glycomics, Sasisekharan and his lab were the first to conduct detailed studies of a class of glycan-degrading enzymes that were revealed to be critical tools in uncovering fundamental biological roles of glycans in significant health conditions, including cancer, cardiovascular biology, and infectious diseases. and swine flu and the need for development of rapid response capabilities for emerging infectious diseases.

Antibody development The Sasisekharan lab in conjunction with the Singapore-MIT Alliance for Research and Technology (SMART) in Singapore focused on responding rapidly to infectious disease outbreaks from both a technical and regulatory perspective, and initiated a series of antibody programs with increasing speed of development. The lab first developed an improved dengue fever antibody, named monoclonal antibody (mAb) 513 that was reported in 2018. The next program was in yellow fever. A yellow fever antibody named TY014 was developed in 2019, an Investigational New Drug (IND) application was filed in seven months. Clinical trial started the next year.

Sasisekharan's lab was the first to produce antibodies for the treatments of influenza A virus and Zika virus infections. The antibody for influenza (H7N9) disease was named VIS410, and the development was reported in the Proceedings of the National Academy of Sciences in 2015. The antibody for Zika virus was called ZAb_FLEP as reported in the Cell Host & Microbe in 2018. An IND was filed for Zika antibody within nine months of initiation.

The most recent program developed a SARS-CoV-2 antibody which went from design to first human infusion in four months in 2020.

Heparin crisis Towards the end of 2007 and early 2008, there were reports of people developing allergic reactions after having an injection of heparin sodium. 150 people died in US, with hundreds of clinical cases in other parts of the world. An investigation by FDA from January 2008 identified that the majority of the drug came from Baxter International. Baxter immediately recalled al its heparin products. The incidence was known as the heparin crisis.

Sasisekharan led the research team that included scientists from MIT, Koch Institute, Center for Drug Evaluation and Research, and Centers for Disease Control and Prevention. The team reported their findings in Nature Biotechnology that heparin was contaminated with over-sulfated chondroitin sulfate, a highly immune activator. In subsequent reports in The New England Journal of Medicine, the team concluded that heparin contaminated with over-sulfated chondroitin sulfate was the cause of adverse effects and deaths.

Entrepreneurial activities Sasisekharan's PhD research led to the development of glycan sequencing platform. With his supervisor, Langer, he established Momenta Pharmaceuticals in 2001,

Sasisekharan also founded Visterra Inc., a company focused on the development of antibody-based treatments for kidney diseases and other hard-to-treat conditions like cancer and infectious. In 2018, Otsuka Pharmaceutical acquired the company for US$430 million. In 2015, he co-founded Tychan, a Singapore-based company for the development of antibodies for infectious diseases such as COVID-19.

Sasisekharan serves on the advisory board for multiple biotechnology companies, venture fundings, and non-profit organizations that are engaged in biotechnological developments. the development of VIS410 reported in the Proceedings of the National Academy of Sciences in 2015 The scientists claimed that research data "show striking similarities" to published data. Data on VIS410 "produces exact matches to an earlier US patent" named Ab044 in 2013, as well as a "remarkable degree of similarity" with FI6v3 that was described in 2011 by a team of European scientists. They also remarked that ZAb_FLEP "leaves little doubt that ZAb_FLEP corresponds to mAb", a patent already filed by Sasisekharan's lab, and a "remarkable sequence similarity" They concluded: "We find it difficult to view these authors’ approach in any light other than an intent to mislead as to the level of originality and significance of the published work." Gerngross took the allegations further and publicly explained in a series of media interviews. and rebuttal to the accusations.

Exoneration The MIT investigation took three and a half years, and the decision was announced in 2023. The MIT Vice President for Research, Maria T. Zuber, released a public statement on 14 March clearing Sasisekharan of the allegation charge, stating that: "MIT has completed its investigation with no finding of research misconduct for any of the submitted allegations." An explanation of the science was immediately provided on the website for the Sasisekharan Lab.

As Sasisekharan was exonerated from the charges of misconduct, the allegations turned the table on the mAbs authors. Peter Dedon, Sasisekharan's colleague, asserted that there are "big concerns" about the mAbs paper. The Adimab is a rival company to Sasisekharan's in antibody research, and Dedon believed that it was an attempt to discredit Sasisekharan for financial advantages, saying, "This is like corporate warfare being waged in an academic journal." As one of the leaders of Adimab, Wittrup was Sasisekharan's colleague, the issue could have been discussed and settled without public accusations.

In 1999, Sasisekharan received the Beckman Young Investigators Award, the Burroughs Wellcome Fund Young Investigator Award in Pharmacological Sciences, and the Edgerly Science Partnership Award. He received the CaPCure Awards from the CaPCure Foundation (now the Prostate Cancer Foundation) in 1998, 1999, 2000, and 2001.

In 2009, Sasisekharan became elected Fellow of the American Institute for Medical and Biological Engineering. He received the MERIT Award from the U.S. National Institute of General Medical Sciences in 2010. In 2014, he became elected Fellow of the U.S. National Academy of Inventors. In 2026, he was elected to the National Academy of Engineering.