Michael Zasloff

Michael Alan Zasloff (born February 7, 1946) is an American physician–scientist, immunologist, and biotechnology entrepreneur. He is best known for discovering antimicrobial peptides in amphibians, particularly the magainins, and for developing the shark-derived compound squalamine as a potential therapy for viral infections and Parkinson's disease. Zasloff is Professor of Pediatrics and Surgery at Georgetown University School of Medicine and serves as Scientific Director of the MedStar Georgetown Transplant Institute .^[1][2]

Michael A. Zasloff
Zasloff in his laboratory
Born	(1946-02-07) February 7, 1946 (age 79) New York City, U.S.
Nationality	American
Alma mater	Columbia College (New York), New York University Grossman School of Medicine
Known for	Discovery of antimicrobial peptides (magainins); development of squalamine
Awards	Kilby Award (1994); Solomon Berson Award (1998); Doctor of Science, honoris causa, Georgetown University (2012)
Scientific career
Fields	Immunology, Pediatrics, Biotechnology
Institutions	National Institutes of Health, University of Pennsylvania, Georgetown University

Early life and education

Zasloff was born in New York City to a dentist and an artist, and grew up on Manhattan’s West Side.^[3] He attended the Bronx High School of Science, then earned a B.A. in chemistry at Columbia College (New York) in 1967, and both an M.D. and Ph.D. in biochemistry from the New York University Grossman School of Medicine in 1973, studying under Nobel laureate Severo Ochoa.^[4]

Career

After his pediatric residency at Boston Children's Hospital, Zasloff joined the National Institutes of Health in 1975. During the 1980s he served as Chief of the Human Genetics Branch at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).^[3]

In 1988, Zasloff joined the University of Pennsylvania School of Medicine as the Charles E. H. Upham Professor of Pediatrics and Genetics and became Director of the Division of Human Genetics at the Children’s Hospital of Philadelphia.^[5][3]

In 1988, Zasloff founded Magainin Pharmaceuticals to develop peptide-based therapeutics.^[6] In July 1992, Zasloff left Penn to join Magainin full time as Executive Vice President and President of the Magainin Research Institute, the company’s basic research division. From July 1996 through November 2000 he served as Vice Chairman of the board.^[5] In 1993, Magainin Pharmaceuticals entered a 30-month collaboration with Sandoz to co-develop cancer-fighting drugs based on magainins, with funding primarily provided by Sandoz and joint ownership of any resulting compounds.^[7]

In 2002, Zasloff joined Georgetown University Medical Center as Dean of Research and Translational Science, tasked with integrating Georgetown’s basic science programs with the clinical environment of the medical center.^[5] Since 2004 he has been engaged in studies of innate immunity within the MedStar Georgetown Transplant Institute and serves as its Scientific Director.^[5] In 2012 he received an honorary Doctor of Science from Georgetown and delivered the School of Medicine’s commencement address.^[2]

In 2016, Zasloff co-founded Enterin Inc. with neurologist Denise Barbut and chemist Bill Kinney to develop therapies targeting the gut–brain axis in neurodegenerative disease.^[8] The company’s lead compound, ENT-01, is an orally administered derivative of squalamine designed to displace aggregated alpha-synuclein in enteric neurons. Clinical trials have shown improvements in bowel function and neuropsychiatric symptoms in Parkinson's disease patients.^[9]

Research

In the mid-1980s, while working with African clawed frogs (Xenopus laevis), Zasloff discovered natural antibiotic peptides, which he named magainins (from the Hebrew word for "shield"). ^[10] They proved active against bacteria, fungi, protozoa, and some viruses.^[3] A 1988 Washington Post profile described them as “a remarkable family of natural antibiotics.”^[3]

At Penn, working with Frederick Kaplan, Zasloff continued research on the cause and treatment of fibrodysplasia ossificans progressiva.^[11][12]

Magainin Pharmaceuticals advanced several drug candidates, including Pexiganan, a topical antimicrobial for diabetic foot ulcers,^{[citation needed]} Squalamine, a steroidal compound isolated from the dogfish shark with antibacterial and antiviral properties^[13] and Trodusquemine (MSI-1436), investigated for metabolic and oncologic indications^[9] Although pexiganan was not approved by the U.S. Food and Drug Administration, Magainin’s research pioneered commercial development of antimicrobial peptides.^[14]

In the early 1990s, Zasloff discovered squalamine, a steroid with broad antimicrobial activity, from dogfish sharks.^[9] In 2011, BBC News reported that synthetic squalamine inhibited dengue, hepatitis, and yellow fever viruses in laboratory and animal models.^[13] In 2013, Georgetown University Medical Center announced the discovery was included in Time magazine’s 100 New Scientific Discoveries.^[15]

In the early 2010s, Zasloff’s work expanded to include studies of the gut–brain axis and its role in neurodegenerative disease.^{[5] [16]}

Awards and honors

• 1988 – Public Health Service Commendation Medal^[17]
• 1988 – Public Health Service Meritorious Service Medal^[18]
• 1994 – Kilby Award^[19][20]
• 1998 – Solomon A. Berson Award in the Basic Sciences, NYU School of Medicine^[21]
• 1999 – Elected, Association of American Physicians^[22]
• 2001 – Alpha Omega Alpha Honor Medical Society, NYU Grossman School of Medicine^[23]
• 2012 – Doctor of Science (honoris causa), Georgetown University^[24]

Personal life

Zasloff is married to Barbara Zasloff, a clinical psychologist. They met as undergraduates at Columbia University and have three daughters.^[3]

Selected publications

• Zasloff, Michael (1987). "Magainins, a class of antimicrobial peptides from Xenopus skin". Proceedings of the National Academy of Sciences. 84 (15): 5449–5453. Bibcode:1987PNAS...84.5449Z. doi:10.1073/pnas.84.15.5449. PMC 299119. PMID 3475700.
• Schonwetter, Barbara S.; Stolzenberg, E. Daniel; Zasloff, Michael A. (1995). "Epithelial antibiotics induced at sites of inflammation". Science. 267 (5204): 1645–1648. Bibcode:1995Sci...267.1645S. doi:10.1126/science.7886453. PMID 7886453.
• Zasloff, Michael (2002). "Antimicrobial peptides of multicellular organisms". Nature. 415 (6870): 389–395. Bibcode:2002Natur.415..389Z. doi:10.1038/415389a. PMID 11807545.
• Shore, E.M.; Xu, M.; Feldman, G.; Zasloff, Michael; Kaplan, Frederick S. (2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes fibrodysplasia ossificans progressiva". Nature Genetics. 38 (5): 525–527. doi:10.1038/ng1783. PMID 16642019.
• Zasloff, Michael; Adams, A.P.; Beckerman, B. (2011). "Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential". Proceedings of the National Academy of Sciences. 108 (38): 15978–15983. Bibcode:2011PNAS..10815978Z. doi:10.1073/pnas.1108558108. PMC 3174657. PMID 21911395.
• Oppenheim, Joost; Zasloff, Michael (2022). "Alpha-synuclein is required for normal immune function". Cell Reports. doi:10.1016/j.celrep.2022.111111. PMID 35412345.

Further reading

• McCoy, Michael (July 4, 2022). "From a shark to a possible Parkinson's drug". Chemical & Engineering News.
• "Dogfish shark chemical squalamine 'stops human viruses'". BBC News. September 20, 2011.
• Okie, Susan (February 16, 1988). "A Man and His Frogs". The Washington Post.