Nussenzweig, Michael C.

Name: Michel C. Nussenzweig
Date of Birth: February 10, 1955
Education:
1975 B.A. – New York University College of Arts and Sciences
1981 Ph.D. – The Rockefeller University
1982 M.D. – New York University School of Medicine
Clinical Training:
1982-1985 Intern & Resident, Internal Medicine, Clinical Fellow, Infectious Diseases Massachusetts General Hospital
Postdoctoral Training:
1986-1989 Harvard Medical School, Department of Genetics
Professional Appointments
1990-1996 Assistant & Associate Professor, The Rockefeller University
1990-1999 Assistant & Associate Investigator, Howard Hughes Medical Institute
1996-present Professor & Senior Physician, The Rockefeller University
1999-present Investigator, Howard Hughes Medical Institute
2000-2013 Sherman Fairchild Professor, The Rockefeller University
2013-present Zanvil A. Cohn & Ralph M. Steinman Professor, The Rockefeller University

For his groundbreaking work demonstrating broad and potent neutralizing antibodies to HIV-1 and establishing that they are a safe and effective immunotherapeutic for infected humans.
Nussenzweig is responsible for key insights into dendritic and B cell function. With Steinman, he opened the field of antigen presentation by DCs by discovering that they capture, process and present antigens to initiate immunity. He produced the first DC-monoclonal antibody that was essential in establishing their role in immune responses and cloned the first endocytic receptor expressed by DCs. Using these reagents he developed a method to deliver antigens to DCs in vivo, leading to the discoveries that in steady state, DCs maintain peripheral tolerance and that different DC subsets have distinct antigen processing capacities. He resolved the long-standing problem of how DCs are related to and diverge from other myeloid cells including monocytes during development in the bone marrow. In recognition of his work with Steinman, Nussenzweig was chosen to deliver the 2011 Nobel lecture in Steinman’s place.
As a fellow with Leder, he used transgenic mice to show that membrane bound antibodies regulate allelic exclusion and lymphocyte development. Nussenzweig’s discovery that antibody class switching activates the DNA damage response opened up a new area of B cell biology. He established the importance of the DNA double strand break response to resolution of the class switch reaction and demonstrated that the same DNA lesions that initiate switching can also lead to oncogenic chromosome translocations between antibody genes and c-myc.
Antibodies are the essential protective elements of nearly all vaccines. In the last several years’ antibodies have also become important therapeutic agents in treating inflammation and cancer. Nussenzweig’s research is on the development and function of antibodies and on the B-lymphocytes that produce them. He developed robust and scalable methods for the cloning of antibody genes from single human B cells. He first applied this approach to define how tolerance develops in normal individuals and later to the HIV-1 antibody problem.
Nussenzweig made a ground breaking advance in this area when he uncovered broad and potent neutralizing antibodies to HIV-1. His work, and that of others that rapidly adopted his methods, led to the discovery of naturally arising anti-HIV antibodies that were orders of magnitude more potent than previously known antibodies. Moreover, they revealed novel targets of HIV-1 vulnerability. The new antibodies neutralized up to 95% of all HIV-1 strains individually, and nearly all known strains when combined even at very low concentrations. Nussenzweig established that these antibodies both prevent and control chronic infection in humanized mice and in macaques. He then confirmed the pre-clinical studies in phase 1 clinical trials in humans. His clinical experiments established that antibodies are a safe and effective for HIV-1 prevention and therapy.
He is a Howard Hughes Investigator, a fellow of the American Academy of Arts and Sciences, the Brazilian Academy of Sciences, a member of the National Academy of Medicine USA, and the National Academy of Sciences USA.