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We're looking at interactions a thousand-fold smaller than the human eye can see with the best light microscope. ”
Patrick Hogan, Ph.D.
Professor
Division of Signaling and Gene Expression
Contact
biography

cell-bullet1.jpg"In the last few years, physics, chemistry, and engineering have given us incisive new tools that can be applied to biological and medical problems.  The challenge is to deploy these tools creatively to increase our understanding of cell biology and to discover treatments for human disease." - Patrick Hogan, Ph.D.

Dr. Hogan, who will join the Institute in early 2010, began his professional career in the Department of Neurobiology at Harvard Medical School, where he headed a research laboratory and taught neurobiology.  In 1996, he moved his laboratory to the Harvard-affiliated Immune Disease Institute, and continued to teach at Harvard College and Harvard Medical School.

Patrick Hogan, Ph.D.
Dr. Hogan is internationally recognized for his work on the calcineurin-NFAT pathway, which regulates gene transcription in many cell types, and for his work on cellular calcium signaling.  He holds baccalaureate and Ph.D. degrees from Harvard.

research focus

cell-bullet2.jpgPatrick Hogan, Ph.D., studies cells at the nano level - seeking to understand how protein-protein interactions on the submicroscopic scale can have gargantuan impacts on human health and disease.  "My laboratory is interested in the processes by which proteins interact with each other and with DNA to turn on genes in the nucleus.  That's the whole secret of how T cells work," he said, referring to the body's infection-fighting white blood cells.  "The interactions we study are subtle but can be the key to human health and disease."  Dr. Hogan researches how calcium entry into T cells turns on the genes that are necessary to fight infections and cancers.  "This flows from my earlier work in neurobiology," he said, "where we tried to understand how pain sensory neurons are activated.  That was my apprenticeship in how calcium and other ions enter cells, and how cells perceive and respond to signals."  His laboratory made a landmark discovery in 2006, when they studied a protein, ORAI1, that was mutated in two children with immune deficiency, making the children unusually susceptible to life-threatening infections.  Dr. Hogan related the immune deficiency directly to calcium by showing that ORAI1 forms the pore of the calcium entry channel in T cells.  "The hopeful lesson we take from these immunodeficient patients is that it may be possible to develop new therapies for transplant rejection and autoimmune disorders by targeting the calcium channel," he said.

selected publications

cell-bullet3.jpgDephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci USA. 2011

Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol. 2011

Pore architecture of the ORAI1 store-operated calcium channel. Proc Natl Acad Sci. USA.
2010

STIM1 gates the store-operated calcium channel ORAI1 in vitro. Nature Structural & Molecular Biology. 2010

Structure of calcineurin in complex with PVIVIT peptide: portrait of a low-affinity signalling interaction. J Mol Biol. 2007

Orai1 is an essential pore subunit of the CRAC channel. Nature. 2006

A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature. 2006  

Structural delineation of the calcineurin-NFAT interaction and its parallels to PP1 targeting interactions. J Mol Biol. 2004 

Selective inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with small organic molecules. Proceedings of the Proc Natl Acad Sci U S A. 2004

Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT. Molecular Cell. 1998

Immunosuppressive drugs prevent a rapid dephosphorylation of the transcription factor NFAT1 in stimulated immune cells. Proc Natl Acad Sci U S A. 1995

Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science. 1993

SELECTED REVIEWS

Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annual Review of Immunology. 2010

Dissecting ICRAC, a store-operated calcium current. Trends in Biochemical Sciences. 2007

Transcriptional regulation by calcium, calcineurin, and NFAT: structural and cell biological aspects. Genes & Development. 2003

View all publications
The link above may include papers by scientists with the same or similar name.

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  • JAMES J. LEE,  "Fifty Shades of Eosin:  The Hidden Role of Eosinophils in Allergic Inflammation"    
    **Thursday 10/30/14
    : 12:00 PM
  • HUI HU,  "TBA"
    Wednesday 11/05/14: 12:00 PM
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