Julie M. Overbaugh is an American virologist. She is a professor at the Fred Hutchinson Cancer Research Center. Overbaugh is best known for her translational approach to studying HIV transmission and pathogenesis and studies of how the antibody response evolves to recognize viruses. Her work in maternal and infant HIV transmission helped make clear the risk posed by breastfeeding and highlighted unique characteristics of an infant immune response that could inform vaccine development. Major scientific contributions to the understanding of HIV transmission and pathogenesis also include: identifying a bottleneck that selects one or a few variants during HIV transmission; demonstrating the importance of female hormones in HIV infection risk; showing the HIV reinfection is common; demonstrating a role for antibodies that mediate ADCC in clinical disease; showing that HIV infected infants develop unique neutralizing antibody responses to HIV.
Overbaugh is an elected member of the National Academy of Sciences and the American Academy of Arts and Sciences. In addition to being recognized for her scientific contributions, she is also recognized for her mentoring, her advocacy for equity and her commitment to global health.
Early life and education Overbaugh was born and raised in Pennsylvania and graduated from Delone Catholic High School in 1975. During high school, she captained their basketball and field hockey teams and received an award for Excellence in Athletics.
Following high school, Overbaugh was recruited to play college basketball for the University of Connecticut's Huskies from 1976 to 1978. During her tenure, she averaged 3.5 points in 46 games, and also played varsity tennis and served as team captain during her final year. She graduated with a Bachelor of Science degree in chemistry in 1979 and earned her PhD in chemistry from the University of Colorado Boulder. During her PhD, Overbaugh spent four months in Oklahoma aiding the effort to ratify the Equal Rights Amendment. She returned to school to complete her PhD and continued her training as a postdoctoral fellow in interdisciplinary programs in health and cancer biology at the Harvard T.H. Chan School of Public Health from 1983 to 1987. During her fellowship, she became interested in HIV research because it was a "clear intersection of science and public health and medicine."
Career Following her fellowship, Overbaugh joined the University of Washington (UW) to expand their HIV research program to include a basic science focus. In 1992, she became a member of the Nairobi HIV/STD Research Project, which included collaborating on a study of HIV mother-infant infection. For this, she joined Joan Kreiss and Ruth W. Nduati in Kenya to understand the risk of HIV transmission through breastfeeding. The research team found that breastfeeding doubled the risk of HIV transmission from mother to child. Nduati R, John G, Mbori-Ngacha D, Richardson B, Overbaugh J, Mwatha A, Ndinya-Achola J, Bwayo J, Onyango FE, Hughes J, Kreiss JK. Effect of breastfeeding and formula feeding on transmission of HIV-1: A randomized clinical trial. JAMA. 283(9): 1167-1174, 2000. Her subsequent studies showed that the levels of virus in breastmilk predicted infection risk. Rousseau CM, Nduati RW, Richardson BA, John-Stewart GC, Mbori-Ngacha DA, Kreiss JK, Overbaugh J. Association of levels of HIV-1-infected breast milk cells and risk of mother-to-child transmission. J Infect Dis. 190(10): 1880-1888, 2004.Rousseau CM, Nduati RW, Richardson BA, Steele MS, John-Stewart GC, Mbori-Ngacha DA, Kreiss JK, Overbaugh J. Longitudinal analysis of human immunodeficiency virus type 1 RNA in breast milk and of its relationship to infant infection and maternal disease. J Infect Dis. 187(5): 741-747, 2003.
Overbaugh left the UW in 1999 to join the Fred Hutchinson Cancer Research Center where she continued and expanded her studies of HIV transmission and pathogenesis, including working closely with the Kenya research collaborative team.. That year Overbaugh received an Elizabeth Glaser Scientist award to expand her studies of mother-infant transmission of HIV to better understand how features of the virus and immune response impact infant infection risk. They went on to define immune factors that impact transmission in the setting of infant exposure, particularly a role for non-neutralizing antibodies that mediated cell killing in infant infection and disease Milligan C, Richardson BA, John-Stewart G, Nduati R, Overbaugh J. Passively acquired antibody–dependent cellular cytotoxicity (ADCC) activity in HIV-infected infants is associated with reduced mortality. Cell Host Microbe.17(4): 500-506, 2015.Yaffe Z, Naimen NE, Slyker J, Wines BD, Richardson BA, Bosire R, Farquhar C, Ngacha M, Nduati R, John-Stewart G, Overbaugh J. Improved HIV-infected infant survival is correlated with high levels of HIV-specific ADCC activity in multiple cohorts. Cell Rep Med. 20;2(4), 2021. Her research team also discovered novel aspects of the infected infant's immune response to HIV and isolated and characterized the first HIV neutralizing antibodies from infants.Goo L, Chohan V, Nduati R, Overbaugh J. Early development of broad neutralizing antibodies in HIV-1 infected infants. Nat Med. 20(6): 655-658, 2014. Simonich CA, Williams KL, Verkerke HP, Williams JA, Nduati R, Lee KK and Overbaugh J. HIV-1 neutralizing antibodies with limited hypermuation from an infant. Cell. 166(1): 77-87, 2016.Simonich C, Doepker L, Duncan R, Williams JA, Dhar A, Yaffe Z, Gentles L, Small CT, Oliver B, Vigdorovich V, Prasad VM, Nduati R, Sather DN, Lee KK, Matsen FA, Overbaugh J. Kappa chain maturation helps drive rapid development of an infant HIV-1 broadly neutralizing antibody lineage. Nat Commu. 10(1): 2190, 2019 They also discovered a variant of HIV in an infant, BG505, that has been extensively leveraged for studies of HIV structure and for vaccine development.1. Wu X, Parast AB, Richardson BA, Nduati R, John-Stewart G, Mbori-Ngacha D, Rainwater SM, Overbaugh J. Neutralization escape variants of human immunodeficiency virus type 1are transmitted from mother to infant. J Virol. 80(2): 835-844, 2006.
Overbaugh's research has also focused on understanding how viral evolution impacts disease and she showed that the viruses that evolve over the course of infection are more pathogenic, in part because they have escaped neutralizing antibody control.Kimata JT, Kuller L, Anderson DB, Dailey P, Overbaugh J. Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression. Nat Med. 5(5): 535-541, 1999.Overbaugh J, Rudensey LR. Alterations in potential sites for glycosylation during evolution of the simian immunodeficiency virus envelope gene in macaques. J Virol. 66(10): 5937-5948, 1992.1. Chackerian B, Rudensey LM, Overbaugh J. Specific N-linked and O-linked glycosylation modifications in the envelope V1 domain of simian immunodeficiency virus variants that evolve in the host alter recognition by neutralizing antibodies. J Virol. 71(10): 7719-7727, 1997. Her work also highlighted that retroviruses can evolve to change their entry receptors and by so doing, can infect new cells and cause changes in disease outcomes.Overbaugh J, Donahue PR, Quackenbush SL, Hoover EA, Mullins JI. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency in cats. Science. 239(4842): 906-910, 1988.Overbaugh J, Riedel N, Hoover EA, Mullins JI. Transduction of endogenous envelope genes by feline leukemia virus in vitro. Nature. 332(6166): 731-734, 1988.Anderson MM, Lauring AL, Burns CC, Overbaugh J. Identification of a cellular cofactor required for infection by feline leukemia virus. Science. 287(5459): 1828-1830, 2000Lauring AS, Anderson MM, Overbaugh J. Specificity in receptor usage by T-cell-tropic feline leukemia viruses: Implications for the in vivo tropism of immunodeficiency-inducing variants. J Virol. 75(19): 8888-8898, 2001. Cheng HH, Anderson MM, Hankenson FC, Johnston L, Kotwaliwale CV, Overbaugh J. Envelope determinants for dual-receptor specificity in feline leukemia virus subgroup A and T variants. J Virol. 80(4): 1619-1628, 2006. Rohn JL, Moser MS, Gwynn SR, Baldwin DN, Overbaugh J. In vivo evolution of a novel, syncytium-inducing and cytopathic feline leukemia virus variant. J Virol. 72(4): 2686-2696, 1998. Mendoza R, Anderson MM, Overbaugh J. A putative thiamine transport protein is a receptor for feline leukemia virus subgroup A. J Virol. 80(7): 3378-3385, 2006. She also discovered that HIV adapted in cell culture can use more diverse receptor othologues, and that this adaption makes strains used in model system distinct Humes D, Overbaugh J. Adaptation of Subtype A Human Immunodeficiency Virus Type 1 Envelope to Pig-Tailed Macaque Cells. J Virol. 85(9): 4409-20, 2011. Humes D, Emery S, Laws E, Overbaugh J. A species-specific amino acid difference in the macaque CD4 receptor restricts replication by global circulating HIV-1 variants representing viruses from recent infection. J Virol. 86(23): 12472-12483, 2012Boyd DF, Sharma A, Humes D, Cheng-Mayer C and Overbaugh J. Adapting SHIVs in vivo selects for Envelope-mediated Interferon- α resistance. PLos Pathog. 12(7): e1005727, 2016. In her very early work, Overbaugh also studied adaptive evolution.Cairns J, Overbaugh J, Miller S. The origin of mutants. Nature. 335(6186): 142-145, 1988.