Ram Sasisekharan

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Ram Sasisekharan
Born
India
Alma mater
  • Harvard Medical School
Known forglycomics, early studies of glycans in significant health conditions
Scientific career
Fields
  • Biomedical Sciences
Institutions
  • Massachusetts Institute of Technology
  • Koch Institute for Integrative Cancer Research

Ram Sasisekharan, Ph.D., (born 1965) is best known for leading the international team that identified oversulfated chondroitin sulfate as a contaminant in the US heparin supply in 2007 and 2008.[1][2][3]

Sasisekharan is a professor of Biological Engineering at the Massachusetts Institute of Technology (MIT) and the current Alfred H. Caspary Professor of Biological Engineering and Health Sciences and Technology at the David H. Koch Institute for Integrative Cancer Research.[4] Sasisekharan is also a principal investigator in the Infectious Diseases Interdisciplinary Research Group of the SMART Centre in Singapore.[5]

Sasisekharan founded six biotech companies and is a named inventor on 205 United States patent applications, and is a named author on 200 manuscripts.[6]

Considered a pioneer of the emerging and essential field of glycomics, Sasisekharan and his lab was 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. [4][7] In addition, Sasisekharan’s approach to studying glycans has led to several technology platforms which launched the company Momenta in 2001 and yielded novel translational applications for disease processes and understanding structure-function relationships. [7] Because of this expertise, the FDA requested Sasisekharan’s assistance during the US heparin crisis. [3]

Work at the Sasisekharan Lab led to an understanding of the mutation risk for Avian or Bird Flu [8] and Swine Flu[9] and the need for development of rapid response capabilities for emerging infectious diseases.[10]

The Sasisekharan Lab in conjunction with 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.[11] This was followed by development of a novel Zika antibody for which an IND application was filed within nine months of initiation.[12] The next program in Yellow fever filed an IND application in seven months.[13] The most recent program developed a SARS-CoV-2 antibody which went from design to first human infusion in four months.[14] The Zika, Yellow Fever and SARS-CoV-2 antibodies each successfully concluded phase 2 human trials.

Background and Personal Life

Sasisekharan was born in India in 1965. His father, V. Sasisekharan (Viswanathan Sasisekharan), is an Indian biophysicist who studied the structure of DNA.[15] 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.[16] 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. [7][15]

Academic background

Dr. 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. [4][17] His advancements as Director led to the establishment of the Institute for Medical Engineering and Sciences (IMES).

Early career

Sasisekharan earned his PhD under the direction of MIT Professor Robert S. Langer who challenged him with the task of characterizing and sequencing the components of heparinase, a critical enzyme that degrades or cuts up the sugars in the heparin family.[15] The enzyme had not previously been cloned, but Sasisekharan devised a novel approach of using polymerase chain reaction (PCR) to clone the enzyme in just eight weeks.[7] This first-in-class cloned enzyme became the subject of Sasisekharan’s first patent, US 5,389,539, which was filed in 1992.[18] This was the first of 24 patents with heparinase in the title. From 2007 to 2008, the 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.[19]

Entrepreneurial activities

He founded six companies, including Cerulean Pharma and Momenta Pharmaceuticals.[4][5][19] Momenta was based on his glycan sequencing platform and was eventually acquired by J&J for USD 6.5 Billion. During his 12-year tenure on Momenta’s board, Sasisekharan provided input on the company’s first commercial drug, which is a low-cost, highly potent version of the blood-thinner Lovenox, which is a low molecular weight heparan (LMWH).[6] To complete development and commercialize this generic version of Lovenox, Momenta formed a collaboration with a division of Novartis.[5]

Sasisekharan, co-founded Cerulean in 2006 to leverage nanopharmaceuticals to target tumors with highly potent chemotherapeutics.[19][20]

Sasisekharan also founded Visterra Inc., a company focused on infectious disease therapeutics that was eventually acquired by Otsuka Pharmaceuticals for USD 0.5 Billion.[4] In addition, he co-founded Tychan Pte., Ltd., which is focused on rapid response to infectious diseases.[5][20]

Sasisekharan serves on the advisory board for multiple biotechnology companies, venture funds, and non-profit institutions engaged in translational life-sciences innovations.[5][20]

References

  1. ↑ Kishimoto, T.K. (June 5, 2008). "Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System". New England Journal of Medicine. Retrieved 12 May 2023.
  2. ↑ Trafton, Anne. "Teams Unravel Heparin Death Mystery". MIT News. Massachusetts Institute of Technology. Retrieved 12 May 2023.
  3. ↑ 3.0 3.1 Kemsley, Jyllian. "Heparin Undone - A consortium of scientists raced against the clock to identify the cause of adverse reactions". Chemical and Engineering News. Retrieved 12 May 2023.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "Ram Sasisekharan, PHD". MIT BE. MIT Biological Engineering. Retrieved 12 May 2023.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "3 Questions: Ram Sasisekharan on Hastening Vaccines and Treatments". MIT News. Massachusetts Institute of Technology. Retrieved 12 May 2023.
  6. ↑ 6.0 6.1 "National Center for Biotechnology Information". National Library of Medicine. Pub Med. Retrieved 12 May 2023.
  7. ↑ 7.0 7.1 7.2 7.3 Saigal, Ranjai (22 March 2005). "Lokvani Talks to Dr. Ram Sasisekharan". Lokvani. Retrieved 12 May 2023.
  8. ↑ Yong, E. (6 June 2013). "Some H5N1 and H7N9 Bird Flue Viruses Could Be Onne Mutation Away from Spreading Efficiently Between Humans". The Scientist. Retrieved 12 May 2023.
  9. ↑ Trafton, Anne (March 9, 2011). "MIT Scientists Identify a Mutation that Could Allow the Flu Virus to Spread Much More Easily - Keeping an Eye on H1N1 2011". Massachusetts Institute of Technology. Retrieved 12 May 2023.
  10. ↑ "Rapid Response". Koch Institute, Department of Biological Engineering. Retrieved 12 May 2023.
  11. ↑ Tharakarman, Kannan (April 8, 2013). "Redesign of a cross-reactive antibody to dengue virus with broad-spectrum activity and increased in vivo potency". PNAS. 110 (17). Retrieved 12 May 2023.
  12. ↑ "World's First Zika Antibody Developed by Singapore Company". TEMASEK. Retrieved 12 May 2023.
  13. ↑ Paules, Catharine (April 13, 2017). "Yellow Fever - Once Again on the Radar Screen in the Americas". New England Journal of Medicine. 376: 1397–1399. Retrieved 12 May 2023.
  14. ↑ "ychan to Begin First Clinical Trials for First Novel Monoclonal Antibody Against COVID-19". BusinessWire. June 10, 2020. Retrieved 12 May 2023.
  15. ↑ 15.0 15.1 15.2 May, Mike (November 2003). "The Sweetest Thing - Ram Sasisekharan's research on sugar structures leads to a new biotech business--and perhaps new cures". Harvard Magazine. Retrieved 12 May 2023.
  16. ↑ "Uma Narayanasami, MD". Massachusetts General Hospital. Retrieved 12 May 2023.
  17. ↑ "Ram Sasisekharan, PhD". Koch Institute for Integrative Cancer Research at MIT. Massachusetts Institute of Technology. Retrieved 12 May 2023.
  18. ↑ "Purification of heparinase I, II, and III from Flavobacterium heparinum". Google Patents. Retrieved 12 May 2023.
  19. ↑ 19.0 19.1 19.2 "Biotech to the Rescue Ram Sasisekharan's startups provide novel methods to fight disease and make better drugs". MIT Technology Review. April 29, 2014. Retrieved 12 May 2023.
  20. ↑ 20.0 20.1 20.2 "Cerulean Pharma - Nanoparticle-Based Drug Delivery". Lux Campital. Retrieved 12 May 2023.

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