Faculty

Scott Hensley, PhD

Professor of Microbiology

Department: Microbiology

Graduate Group Affiliations

Contact information

402A Johnson Pavilion
3610 Hamilton Walk
Philadelphia, PA 19104

Office: 215-573-3756
Lab: 215-573-3877

Email:
hensley@pennmedicine.upenn.edu

Publications

Search PubMed for articles

Education:
BA (Biology)
University of Delaware, 2000.
PhD (Cell and Molecular Biology)
University of Pennsylvania, 2006.

Links
Search PubMed for articles

Permanent link

> Perelman School of Medicine > Faculty > Details

Description of Research Expertise

Research Interests
-influenza virus
-H5N1
-SARS-CoV-2
-antibodies
-antigenic drift

Key words: Influenza virus, H5N1, SARS-CoV-2, antigenic drift, viral pathogenesis, viral receptors, antibody specificity, vaccines

Description of Research

Seasonal influenza viruses pose a major threat to the human population. Influenza viruses rapidly escape pre-existing humoral immunity by accumulating mutations in the viral surface proteins hemagglutinin and neuraminidase. This process, termed “antigenic drift”, creates antigenically distinct viruses, making it difficult to predict which types of viruses will predominate during any given flu season. Antigenic drift is a problem for vaccine manufacturers.

Influenza viruses can also cause pandemics. Currently, H5N1 viruses are widely circulating in birds and have recently jumped into dairy cattle within the United States. It is important to monitor the spread of influenza viruses with pandemic potential and to assess the pandemic risk of individual influenza virus strains.

The Hensley laboratory is completing experiments to 1) better understand mechanisms that promote antigenic drift of influenza viruses, 2) assess population immunity against new influenza viral strains with pandemic potential, (3) determine how childhood influenza exposures influence immune responses against seasonal and pandemic influenza strains, (4) better understand heterogeneity in immune responses elicited by influenza vaccines, (5) develop new influenza vaccine platforms, (6) understand how SARS-CoV-2 evolves in a population with heterogenous immunity. Our overarching goals are to use basic immunological and virological approaches to improve viral vaccines and therapeutics.

Enthusiastic undergraduate, graduate, and postdoctoral fellows should email hensley@pennmedicine.upenn.edu if you are interested in joining the lab.

Lab members:

Elizabeth Drapeau, PhD (Penn-CEIRR Coordinator)
Leann Good (Penn-CEIRR Administrative Coordinator)
Tachianna Griffiths (Penn-CEIRR Clinical Coordinator)
Jefferson Santos, PhD (Staff scientist)
Naiqing Ye (Lab manager/research assistant)
Reilly Atkinson (Research assistant)
Jiaojiao Liu, PhD, (postdoctoral fellow)
Gabby Scher (postdoctoral fellow)
Ross England, MD/PhD (CHOP clinical fellow)
Ashley Sobel Leonard, MD/PhD (CHOP clinical fellow)
Rachel Serafin (PhD student/IGG)
Lydia Mendoza (PhD student/MVP)
Grace Li (PhD student/MVP)
Jordan Ort (PhD student/MVP)
Sydney Gang (PhD student/PGG)
Katelyn Amero (PhD rotation student/MVP)
Lucie Song (undergraduate)

Selected Publications

Santos JJS, Wang S, McBride R, Adams L, Harvey R, Zhao Y, Wrobel AG, Gamblin S, Skehel J, Lewis NS, Paulson JC, Hensley SE.: Bovine H5N1 binds poorly to human-type sialic acid receptors. Nature 2025.

Garretson TA, Liu J, Li SH, Scher G, Santos JJS, Hogan G, Vieira MC, Furey C, Atkinson RK, Ye N, Ort JT, Kim K, Hernandez KA, Eilola T, Schultz DC, Cherry S, Cobey S, Hensley SE.: Immune history shapes human antibody responses to H5N1 influenza viruses. Nat Med Mar 2025.

Lowen AC, Baker AL, Bowman AS, García-Sastre A, Hensley SE, Lakdawala SS, Moncla LH, Nelson MI, Pekosz A, Poulson RL, Puryear WB, Runstadler JA, Sutton TC, Tompkins SM, Webby RJ; Risk Assessment Pipeline working group of the NIAID Centers of Excellence for Influenza Research and Response (CEIRR) Network.: Pandemic risk stemming from the bovine H5N1 outbreak: an account of the knowns and unknowns. J Virol 99: e0005225, Apr 2025.

Furey C, Scher G, Ye N, Kercher L, DeBeauchamp J, Crumpton JC, Jeevan T, Patton C, Franks J, Rubrum A, Alameh MG, Fan SHY, Phan AT, Hunter CA, Webby RJ, Weissman D, Hensley SE.: Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus. Nat Commun 15: 4350, May 2024.

Sobel Leonard A, Mendoza L, McFarland AG, Marques AD, Everett JK, Moncla L, Bushman FD, Odom John AR, Hensley SE.: Within-host influenza viral diversity in the pediatric population as a function of age, vaccine, and health status. Virus Evol 10: veae034, Apr 2024.

Goodwin E, Gibbs JS, Yewdell JW, Eisenlohr LC, Hensley SE.: Influenza virus antibodies inhibit antigen-specific de novo B cell responses in mice. J Virol 98: e0076624, Sep 2024.

Johnston TS, Li SH, Painter MM, Atkinson RK, Douek NR, Reeg DB, Douek DC, Wherry EJ, Hensley SE.: Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants. Immunity 57: 912-925, Apr 2024.

England RN, Drapeau EM, Alameh MG, Hosseinzadeh R, Weissman D, Hensley SE.: Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model. NPJ Vaccines 9: 110, Jun 2024.

Bolton MJ, Santos JJS, Arevalo CP, Griesman T, Watson M, Li SH, Bates P, Ramage H, Wilson PC, Hensley SE.: IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding. Proc Natl Acad Sci U S A 120: e2216521120, Aug 2023.

Gouma S, Furey C, Santos JJS, Parkhouse K, Weirick M, Muramatsu H, Pardi N, Fan SHY, Weissman D, Hensley SE.: Nucleoside-Modified mRNA-Based Influenza Vaccines Circumvent Problems Associated with H3N2 Vaccine Strain Egg Adaptation. J Virol 97: e0172322, Jan 2023.

Bolton MJ, Ort JT, McBride R, Swanson NJ, Wilson J, Awofolaju M, Furey C, Greenplate AR, Drapeau EM, Pekosz A, Paulson JC, Hensley SE.: Antigenic and virological properties of an H3N2 variant that continues to dominate the 2021-22 Northern Hemisphere influenza season. Cell Reports 39: 110897, May 2022.

Christensen SR, Martin ET, Petrie JG, Monto AS, Hensley SE.: The 2009 Pandemic H1N1 Hemagglutinin Stalk Remained Antigenically Stable after Circulating in Humans for a Decade. Journal of Virology May 2022.

Pierce CA, Herold KC, Herold BC, Chou J, Randolph A, Kane B, McFarland S, Gurdasani D, Pagel C, Hotez P, Cobey S, Hensley SE.: COVID-19 and children. Science 377: 1144-1149, Sep 2022.

Anderson EM, Li SH, Awofolaju M, Eilola T, Goodwin E, Bolton MJ, Gouma S, Manzoni TB, Hicks P, Goel RR, Painter MM, Apostolidis SA, Mathew D, Dunbar D, Fiore D, Brock A, Weaver J, Millar JS, DerOhannessian S; UPenn COVID Processing Unit, Greenplate AR, Frank I, Rader DJ, Wherry EJ, Bates P, Hensley SE.: SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared with SARS-CoV-2 mRNA vaccinations. Cell Rep 41: 111496, Oct 2022.

Arevalo CP, Bolton MJ, Le Sage V, Ye N, Furey C, Muramatsu H, Alameh MG, Pardi N, Drapeau EM, Parkhouse K, Garretson T, Morris JS, Moncla LH, Tam YK, Fan SHY, Lakdawala SS, Weissman D, Hensley SE.: A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 378: 899-904, Nov 2022.