PRESIDENT'S DISTINGUISHED LECTURER I

Sing Sing Way, MD, PhD
Pauline and Lawson Reed Chair, Division of Infectious Diseases
Professor, UC Department of Pediatrics
Cincinnati, OH, USA

Thursday, March 23, 2023
8:10 a.m. - 9:00 a.m.

Dr. Sing Sing Way has made seminal contributions to reproductive and developmental immunology with direct relevance to improving pregnancy outcomes and the health of infants. His laboratory pioneered tools for tracking immune components with fetal-specificity, and utilized these tools to reveal fundamental insights as to how pregnancy immunologically works. This includes distinctions between immune tolerance versus rejection driving the pathogenesis of pregnancy complications and how mothers immunological remember their babies as a basis for how prior pregnancy impacts the susceptibility of women to complications in future pregnancies. His group showed hypo-responsiveness of neonatal immune cells reflects of active suppression, as opposed to immaturity, and the importance of suppression allowing babies to tolerate first commensals. Integrating the maternal-fetal dyad, he showed the importance of microchimeric cells naturally transferred between mothers and babies in optimizing reproductive outcomes, and how antibodies are structurally changed by pregnancy to expand their protective scope upon vertical transfer.

Dr. Way is an infectious disease pediatrician with an innate and contagious passion for discovery to improve human health. His education began at UC Berkeley where he worked with Dr. Paul Bartlett synthesizing small molecule inhibitors against key biosynthetic enzymes in Mycobacterium tuberculosis. Later matriculating into the combined MD-PhD program at Albert Einstein College of Medicine originally with the goal of continuing this work in synthetic biological chemistry towards designing improved antimicrobial compounds, his approach changed dramatically under the influence of Dr. Barry Bloom who pointed out that vaccines can provide more durable protection against infection. His doctorate thesis summarized in 5 first author publications the mediators of protective immunity to Shigella flexneri infection further defined distinctions in how immune components defend against pathogens that live within compared with outside of cells. After clinical residency training in pediatrics, additional training was with Dr. Christopher Wilson characterizing differences in how neonatal compared with adult immune cells respond to infection. This work has been carried through in his own laboratory over the past 15 years to not only make fundamental insights as to how neonatal immune components work, but also moving the scope of investigation to the underlying pathogenesis of pregnancy complications and fundamental discoveries for how tissues on both sides of the placenta are linked through the maternal-fetal immunological dyad. His leadership role in these areas has been recognized by the Howard Hughes Medical Institute Faculty Scholar Award, NIH Director’s Pioneer award, the inaugural recipient of the Drukier Prize in Children’s Health research, and E. Mead Johnson Award from the Society of Pediatric Research.

Key publications that highlight Dr. Way’s work in reproductive and developmental biology include.

1. Erickson JJ, Archer-Hartmann S, Yarawshy AE, Miller JLC, Seveau S, Shao T-Y, Severance AL, Miller-Handley H, Wu Y, Pham G, Waski BR, Parrish CR, Hu, YC, Lau JTY, Azadi P, Herr AB, Way SS (2022) Pregnancy enables antibody protection against intracellular infection. Nature 606: 769-775. PMID 35676476
2. Gregory EJ, Liu J, Miller-Handley H, Kinder JM, Way SS (2021) Epidemiology of pregnancy complications through the lens of immunological memory. Front Immunol 12:693189. PMID 34248991
3. Kollmann TR, Marchant A, Way SS (2020) Vaccination strategies to enhance immunity in neonates. Science 368:612-615 PMID 32381718 
4. Kinder JM, Turner L, Stelzer I, Burg AR, Shao TY, Pham G, Way SS (2020) CD8+ T cell functional exhaustion overrides pregnancy induced fetal antigen alloimmunization. Cell Reports 31: 107784. PMID 32579916 
5. Deshmukh H, Way SS (2019) Immunological basis for recurrent fetal loss and pregnancy complications. Annu Rev Pathol Mech Dis 14:185-210. PMID: 30183507
6. Schlaudecker EP, Ambroggio L, McNeal MM, Finkelman FD, Way SS (2018) Declining responsiveness to influenza vaccination with progression of human pregnancy. Vaccine 36:4734-4741. PMID: 29941326
7. Kinder JM, Stelzer IA, Arck PC, Way SS (2017) Immunological implications of pregnancy-induced microchimerism. Nat Rev Immunol 17:483-494. PMID 2848089
8. Kinder JM, Jiang, TT, Ertelt JM, Xin L, Strong BS, Shaaban AF, Way SS (2015). Cross- generational reproductive fitness enforced by microchimeric maternal cells. Cell 162:505-515. PMID 26213383
9. Chaturvedi V, Ertelt JM, Jiang TT, Kinder JM, Xin L, Owens KJ, Jones HN, Way SS (2015). CXCR3 blockade protects against Listeria monocytogenes infection induced fetal wastage. J Clin Invest 125: 328-334. PMID 25751061
10. Elahi S, Ertelt JM, Kinder JM, Jiang TT, Zhang X, Xin L, Chaturvedi V, Strong BS, Qualls JE, Steinbrecher KA, Kalfa TA, Shaaban AF, Way SS (2013). Immune suppressive CD71 erythroid cells compromise neonatal host defense against infection. Nature 504:158-162. PMID 24196717
11. Rowe JH, Ertelt JM, Xin L, Way SS (2012). Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 490: 102-106. PMID 23023128
12. Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS (2011). Foxp3⁺ regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens Cell Host Microbe 10:54-64. PMID 21767812