Jeremy Kamil, PhD
Associate Professor of Microbiology and Immunology
Bachelor of Arts, General Biology - Cornell University
PhD, Microbiology - University of California at Davis
Post-Doctoral Fellowships - Cornell University and Harvard Medical School
August, 2022. Congratulations to Hongbo Zhang and Anthony Domma for their recent publication in mBio. "The Akt Forkhead Box O Transcription Factor Axis Regulates Human Cytomegalovirus Replication"
Congrats to Anthony Domma for winning a travel award to attend the American Society for Virology Conference in July, 2022.
Congrats to recent Kamil Lab graduate Dr. Christopher Nguyen, who finished his PhD requirements in September 2019 and recently started a job at Voyager Therapeutics in Cambridge, MA.
Kudos to Postdoc Fellow Dr. Hongbo Zhang whose first author manuscript was recently accepted at mBio (November 2019).
Major Research Interest
Human Cytomegalovirus (HCMV)
The Kamil laboratory is focused on human cytomegalovirus (HCMV), a beta-herpesvirus that is a leading cause of birth defects and of life-threatening infections in the immunocompromised. Dr. Kamil’s group employs molecular genetic and pharmacological approaches to tackle basic research questions concerning virus biology. NIH-sponsored projects in the Kamil laboratory concern HCMV cell tropism and the regulation of viral gene expression during myeloid cell differentiation. Our work on viral cell tropism stems from an interest in the viral endoplasmic reticulum (ER)-resident protein UL148, which influences the expression of a viral glycoprotein complex required for cell entry. Intriguingly, UL148 is also an immuneëvasin that impedes cell surface presentation of CD58. Recent findings from the lab indicate that UL148 activates an ancient ER stress response pathway called the unfolded protein response (UPR). The data suggest that UL148 stabilizes a viral glycoprotein called “gO” by interfering with ER-associated degradation (ERAD), a cellular pathway that removes misfolded proteins from the ER. Moreover, the observation that UL148 activates the UPR may prove relevant for understanding immune evasion mechanisms. Dr. Kamil’s areas of expertise include viral replication, viral protein kinases, protein-protein interactions, antiviral drug targets, ERAD, UPR, and proteostasis, cell stress responses, cell-cycle regulation, tumor suppressors, viral glycoproteins, and HCMV cell entry.
Human cytomegalovirus replication, regulation of viral cell tropism Human cytomegalovirus (CMV) is a widespread herpesvirus that infects a majority of the human population. Although CMV does not usually cause disease in healthy people, the virus often crosses the placenta to infect the developing fetus, which can result in serious birth defects. In addition, CMV causes life threatening infections in immunocompromised patients. A major goal of our laboratory is to help develop a better understanding of this complex viral pathogen. In 2015, we identified a virally-encoded glycoprotein, UL148, that impacts the virus’ ability to infect different types of human cells. UL148 modulates the expression of alternative viral glycoprotein complexes that play key roles in cell entry, which likely explains its effects on cell tropism. UL148 resides in the endoplasmic reticulum (ER), an organelle at which proteins destined for secretion are first synthesized, folded, and processed before they can be transported further along the secretory pathway. During infection, UL148 stabilizes a subset of newly synthesized viral glycoproteins before they mature beyond the ER to become incorporated into virions. In particular, UL148 regulates the abundance of multi-subunit glycoprotein complexes that are built upon a viral glycoprotein called glycoprotein H (gH), which is a central component of the cell entry machinery shared by all herpesviruses and an important target for the vaccines. Another set of projects in the lab are focused on trying to understand how the virus regulates its genes during infection. In certain cell types, CMV rapidly undergoes lytic replication, during which huge amounts of viral macromolecules are produced to drive the assembly and release of progeny virions, and the host cell is ultimately destroyed as a result. In other cell types, however, the virus persists in a largely silent state called “latency.” We are currently investigating how viral and cellular protein kinases work together to control whether or not the virus actively replicates.
- Oguntuyo KY, Stevens CS, Hung CT, Ikegame S, Acklin JA, Kowdle SS, Carmichael JC, Chiu HP, Azarm KD, Haas GD, Amanat F, Klingler J, Baine I, Arinsburg S, Bandres JC, Siddiquey MNA, Schilke RM, Woolard MD, Zhang H, Duty AJ, Kraus TA, Moran TM, Tortorella D, Lim JK, Gamarnik AV, Hioe CE, Zolla-Pazner S, Ivanov SS, Kamil JP, Krammer F, Lee B. Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera. mBio. 2021 Feb 16;12(1) PubMed PMID: 33593976. https://mbio.asm.org/content/12/1/e02492-20.long
- Hodcroft EB, Domman DB, Snyder DJ, Oguntuyo K, Van Diest M, Densmore KH, Schwalm KC, Femling J, Carroll JL, Scott RS, Whyte MM, Edwards MD, Hull NC, Kevil CG, Vanchiere JA, Lee B, Dinwiddie DL, Cooper VS, Kamil JP. Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677. medRxiv. 2021 Feb 14; PubMed Central PMCID: PMC7885944. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885944/
- Zeller M, Gangavarapu K, Anderson C, Smither AR, Vanchiere JA, Rose R, Dudas G, Snyder DJ, Watts A, Matteson NL, Robles-Sikisaka R, Marshall M, Feehan AK, Sabino-Santos G, Bell-Kareem A, Hughes LD, Alkuzweny M, Snarski P, Garcia-Diaz J, Scott RS, Melnik LI, Klitting R, McGraw M, Belda-Ferre P, DeHoff P, Sathe S, Marotz C, Grubaugh N, Nolan DJ, Drouin AC, Genemaras KJ, Chao K, Topol S, Spencer E, Nicholson L, Aigner S, Yeo GW, Farnaes L, Hobbs CA, Laurent LC, Knight R, Hodcroft EB, Khan K, Fusco DN, Cooper VS, Lemey P, Gardner L, Lamers SL, Kamil JP, Garry RF, Suchard MA, Andersen KG. Emergence of an early SARS-CoV-2 epidemic in the United States. medRxiv. 2021 Feb 8; PubMed Central PMCID: PMC7872376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872376/
- Oguntuyo KY, Stevens CS, Siddiquey MN, Schilke RM, Woolard MD, Zhang H, Acklin JA, Ikegame S, Hung CT, Lim JK, Cross RW, Geisbert TW, Ivanov SS, Kamil JP, Lee B. In plain sight: the role of alpha-1-antitrypsin in COVID-19 pathogenesis and therapeutics. bioRxiv. 2020 Aug 15; PubMed Central PMCID: PMC7430570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7430570/
- Zhang H, Read C, Nguyen CC, Siddiquey M, Shang C, Hall CM, von Einem J, and JP Kamil. In Press. 2019. The human cytomegalovirus nonstructural glycoprotein UL148 reorganizes the endoplasmic reticulum. mBio. Preprint: bioRxiv 641068; doi: https://doi.org/10.1101/641068
- Collins-McMillen D, Rak M, Kamil JP, Moorman NJ, and Goodrum FD. 2019. Alternative Promoters Drive Human Cytomegalovirus Reactivation from Latency. 2019. Proc. Natl. Acad. Sci., U.S.A. https://www.pnas.org/content/116/35/17492
- Siddiquey M, Zhang, H, Nguyen CC, Domma A, and JP Kamil. 2018. The human cytomegalovirus ER resident glycoprotein UL148 activates the unfolded protein response. J. Virol. 92 (20): e00896-18. https://jvi.asm.org/content/92/20/e00896-18
- Li G, Nguyen CC, Ryckman BJ, Britt WJ, and JP Kamil. 2015. A viral regulator of glycoprotein complexes contributes to human cytomegalovirus cell tropism. Proc. Natl. Acad. Sci., U.S.A. 112:4471-6. https://www.pnas.org/content/112/14/4471
See more publications at https://pubmed.ncbi.nlm.nih.gov/?term=jeremy+kamil&sort=date
MEET OUR TEAM
Jeffery Nurdin, MD, PhD
MD, Universitas Airlangga, 2015
PhD, Virology, Research Institute for Microbial Diseases, Osaka University, Japan, 2022
Research: Dr. Nurdin is leading three projects in the lab. The first of these concerns how human cytomegalovirus (HCMV) exploits glycobiology to evade neutralizing antibodies. His second project looks at the roles of FoxO transcription factors during infection. Finally, Dr. Nurdin is also investigating SARS-CoV-2 Spike evolution vis-á-vis trade-offs between Spike stability, antibody evasion and fusogenicity.
Anthony J. Domma
BS, Louisiana State University, 2017
Research: Anthony Domma is investigating how HCMV inactivates the PI3K-Akt pathway during infection, which has implications for understanding how the virus promotes FoxO transcription factor activity during infection and/or reactivation from latency. Anthony also has interests in UL148, a viral ER remodeling protein.
BS, Biological Sciences, Louisiana State University - Shreveport, 2020
Research: Human cytomegalovirus (HCMV) relies on viral glycoprotein complexes that orchestrate membrane fusion events required to deliver the viral genome to host cells. Unsurprisingly, viral entry triggers innate antiviral defenses, such as type I interferons. However, HCMV circumvents antiviral defenses, progresses throughout its lifecycle, and establishes infection. My project tests the hypothesis that certain HCMV glycoproteins enable viral entry in the face of antiviral defense signals.
Dr. Mohammed N. Siddiquey
Dr. Siddiquey is working to identify the roles UL148 in HCMV cell tropism. He will also be involved in projects concerning mechanisms of viral gene regulation in HCMV.