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
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.
- 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