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Patrick Collins, PhD

Instructor, Pathology & Immunology

Phone314-362-5524

Emailplcollins@wustl.edu

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Education

  • BS, Biology: New Mexico Institute of Mining and Technology, Socorro, NM (2006)
  • PhD, Immunology: Vanderbilt University, Nashville, TN (2011)

Research Interests

Primary research focus: Repair of double strand breaks in a chromatin environment

Healthy cells must constantly repair DNA damage from both exogenous and endogenous sources in order to protect the genome from oncogenic mutations. The most dangerous kind of damage is the double strand break (DSB), which can be inappropriately processed into both mutations and translocations. Successful resolution of a DSB depends upon the phosphorylation of surrounding H2Ax-containing nucleosomes (P-H2Ax) which is propagated for several hundred kb to several Mb away form a break and is functionally the base of the chromatin repair platform. As such, broken ends without H2Ax drift apart at high frequencies and are subject to increased levels of resection. By studying the extent of P-H2Ax chromatin revision surrounding a DNA break we hope to understand the basic mechanisms of break repair, and how the healthy cell protects itself against potentially oncogenic mutations.

Epigenetic analysis of human innate lymphocyte cells

Upon sensing pathogens or other alterations to their local microevironments, innate lymphoid cells (ILCs) respond with rapid and robust secretion of cytokines. In turn, these cytokines promote the release of antimicrobial peptides, minimize damage to surrounding cells, and influence the balance of T helper (Th) lymphocytes. While development kinships, functions, and pathologies involving ILCs have been studied extensively in model organisms, little is known about these first responders in humans. Moreover, while ILC and Th subsets rely on common effector genes, distinct signals and kinetics regulate expression programs in innate and cellular counterparts. In 2016, in collaboration with Marco Colonna’s laboratory, we published an integrated “–omics” analyses of lymphoid cells from a human mucosal environment (tonsils). We demonstrated that expression programs for ILC, Th, and NK cells diverge developmentally, but their regulomes devoted to functional polarization are highly convergent. Genes critical for cell-type identity, as well as autoimmune disease-associated polymorphisms, were located in cell-type specific regions of hyperacetylated chromatin known as “super enhancers.” Our results implicated novel pathways for the regulation of genes involved in ILC and Th functional niches, as well as new connections between autoimmune-associated variants and each of the human lymphoid subsets.

Service to the University

2016-2017 Founding Seminar Coordinator: DNA Damage and Metabolism Student Work in Progress

 

Publications

Collins, Patrick L., Shaojing Chang, Melodie Henderson, Mohammed Soutto, Georgia M. Davis, Allyson G. McLoed, Michael J. Townsend, Laurie H. Glimcher, Douglas P. Mortlock, and Thomas M. Aune. “Distal regions of the human IFNG locus direct cell type-specific expression.” The Journal of Immunology 185, no. 3 (2010): 1492-1501.
Hoek, Kristen L., Laura E. Gordy, Patrick L. Collins, Vrajesh V. Parekh, Thomas M. Aune, Sebastian Joyce, James W. Thomas, Luc Van Kaer, and Eric Sebzda. “Follicular B cell trafficking within the spleen actively restricts humoral immune responses.” Immunity 33, no. 2 (2010): 254-265.
Spurlock, Charles F., Zachary T. Aune, John T. Tossberg, Patrick L. Collins, Jessica P. Aune, Joseph W. Huston, Philip S. Crooke, Nancy J. Olsen, and Thomas M. Aune. “Increased sensitivity to apoptosis induced by methotrexate is mediated by JNK.” Arthritis & Rheumatism 63, no. 9 (2011): 2606-2616.
Collins, Patrick L., Melodie A. Henderson, and Thomas M. Aune. “Diverse functions of distal regulatory elements at the IFNG locus.” The Journal of Immunology 188, no. 4 (2012): 1726-1733.
Collier, Sarah P., Patrick L. Collins, Christopher L. Williams, Mark R. Boothby, and Thomas M. Aune. “Cutting edge: influence of Tmevpg1, a long intergenic noncoding RNA, on the expression of Ifng by Th1 cells.” The Journal of Immunology 189, no. 5 (2012): 2084-2088.
Collins, Patrick L., Melodie A. Henderson, and Thomas M. Aune. “Lineage-specific adjacent IFNG and IL26 genes share a common distal enhancer element.” Genes and immunity 13, no. 6 (2012): 481-488.
Aune, Thomas Martin, Patrick L. Collins, Sarah P. Collier, Melodie A. Henderson, and Shaojing Chang. “Epigenetic Activation and Silencing of the Gene that Encodes IFN-γ.” Frontiers in immunology 4 (2013): 112.
Gopalakrishnan, Suhasni, Patrick L. Collins, and Eugene M. Oltz. “Control of Ig gene assembly: lessons from premature activation.” The EMBO journal 32, no. 10 (2013): 1350-1351.
Collins, Patrick L., and Eugene M. Oltz. “Histone methylation keeps the brakes on autophagy.” Molecular and cellular biology 33, no. 20 (2013): 3974-3975.
Pabbisetty, Sudheer K., Whitney Rabacal, Damian Maseda, Delphine Cendron, Patrick L. Collins, Kristen L. Hoek, Vrajesh V. Parekh, Thomas M. Aune, and Eric Sebzda. “KLF2 is a rate-limiting transcription factor that can be targeted to enhance regulatory T-cell production.” Proceedings of the National Academy of Sciences 111, no. 26 (2014): 9579-9584.
Collins, Patrick L., Katherine E. Kyle, Takeshi Egawa, Yoichi Shinkai, and Eugene M. Oltz. “The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes.” Proceedings of the National Academy of Sciences 112, no. 27 (2015): 8367-8372.
Kaiko, Gerard E., Stacy H. Ryu, Olivia I. Koues, Patrick L. Collins, Lilianna Solnica-Krezel, Edward J. Pearce, Erika L. Pearce, Eugene M. Oltz, and Thaddeus S. Stappenbeck. “The colonic crypt protects stem cells from microbiota-derived metabolites.” Cell (2016).
Koues, Olivia I.*, Patrick L. Collins*, Marina Cella*, Michelle L. Robinette*, Sofia I. Porter, Sarah C. Pyfrom, Jacqueline E. Payton, Marco Colonna, and Eugene M. Oltz. “Distinct Gene Regulatory Pathways for Human Innate versus Adaptive Lymphoid Cells.” Cell 165, no. 5 (2016): 1134-1146.


Lab Phone: 314-362-5524
Office Location: CSRB, Room 7730