Hogan Lab

Hogan Lab

"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. // Professor
Division of Signaling and Gene Expression

Overview

Patrick 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.

From The Lab

Mar 14, 2017

The molecular underpinnings of T cell exhaustion

Dec 6, 2015

Matchmaker lets calcium flow

Jun 23, 2013 // San Diego Union Tribune

T cell trigger found

Jun 23, 2013

La Jolla Institute discovers new player critical to unleashing T cells against disease

Hogan Lab

Publications

J Leukoc Biol

Transcriptional and epigenetic regulation of T cell hyporesponsiveness

2017-06
Pereira RM, Hogan PG, Rao A, Martinez GJ
Cell Calcium

Calcium-NFAT transcriptional signalling in T cell activation and T cell exhaustion

2017-05
Hogan PG
Proc Natl Acad Sci USA

Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells

2017-03
Mognol GP, Spreafico R, Wong V, Scott-Browne JP, Togher S, Hoffmann A, Hogan PG, Rao A, Trifari S
eLife

Near-infarared photoactivatable control of Ca(2+) signaling and optogenetic immunomodulation

2015-12
He L, Zhang Y, Ma G, Tan P, Li Z, Zang S, Wu X, Jing J, Fang S, Zhou L, Wang Y, Huang Y, Hogan PG, Han G, Zhou Y
Proceedings of the National Academy of Sciences of the United States of America

TMEM110 regulates the maintenance and remodeling of mammalian ER-plasma membrane junctions competent for STIM-ORAI signaling

2015-12
Quintana A, Rajanikanth V, Farber-Katz S, Gudlur A, Zhang C, Jing J, Zhou Y, Rao A, Hogan PG
Cell Calcium

The STIM1-ORAI1 microdomain

2015-10
Hogan PG
Nature Cell Biology

Proteomic mapping of ER-PM junctions identifies STIMATE as a regulator of Ca(2+) influx

2015-10
Jing J, He L, Sun A, Quintana A, Ding Y, Ma G, Tan P, Liang X, Zheng X, Chen L, Shi X, Zhang SL, Zhong L, Huang Y, Dong…
Journal of General Physiology

Sphingomyelin, ORAI1 channels, and cellular Ca2+ signaling

2015-09
Hogan PG
Biochemical and Biophysical Research Communications

Store-operated calcium entry: mechanisms and modulation

2015-04
Hogan PG, Rao A
Nature Communications

STIM1 triggers a gating rearrangement at the extracellular mouth of the ORAI1 channel

2014-10
Gudlur A, Quintana A, Zhou Y, Hirve N, Mahapatra S, Hogan PG
Journal of Medicinal Chemistry

Structure-based optimization of a peptidyl inhibitor against calcineurin-nuclear factor of activated T cell (NFAT) interaction

2014-09
Qian Z, Dougherty PG, Liu T, Oottikkal S, Hogan PG, Hadad CM, Pei D
Proceedings of the National Academy of Sciences of the United States of America

ORAI1 calcium channel orchestrates skin homeostasis

2013-12
Vandenberghe M, Raphaël M. Lehen'ki V, Gordienko D, Hastie R, Oddos T, Rao A, Hogan PG, Skyrma R, Prevarskaya N
Nature Structural & Molecular Biology

Initial activation of STIM1, the regulator of store-operated calcium entry

2013-08
Zhou Y, Srinivasan P. Razavi S, Seymour S, Meraner P, Gudiur A. Stathopulos PB, Ikura M, Rao A, Hogan PG
Nature

An siRNA screen for NFAT activation identifies septins as coordinators of store-operated Ca2+ entry

2013-07
Sharma S, Quintana A, Findlay GM, Mettlen M, Baust B, Jain M, Nilsson R, Rao A, Hogan PG
Nature

Modulation of TET2 expression and 5-methylcytosine oxidation by the CXXC domain protein IDAX

2013-05
Ko M, Bandukwala HS, Chavez L, Aijö T, Pastor WA, Segal MF, Li H, Koh KP, Lähdesmäki H, Hogan PG, Aravind L, Rao A
Cell Research

Insights into CRAC channel gating and ion permeation

2012-07
Hogan PG
Nature Structural & Molecular Biology

Balanced interactions of calcineurin with AKAP79 regulate Ca2+-calcineurin-NFAT signaling

2012-02
Li H, Pink MD, Murphy JG, Stein A, Dell'Acqua ML, Hogan PG
Proceedings of the National Academy of Sciences of the United States of America

Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex

2011-07
Sharma S, Findlay GM, Bandukawala HS, Oberdoerffer S, Baust B, Li Z, Schmidt V, Hogan PG, Sacks DB, Rao A
Trends in Cell Biology

Interaction of calcineurin with substrates and targeting proteins

2011-02
Li H, Rao A, Hogan PG
Current Topics in Membranes

STIM-ORAI interactions that control the CRAC channel

2017-09
Gudlur A, Zhou Y, Hogan PG

Principal Investigator

Patrick Hogan, Ph.D.

Professor

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.

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.

Lab Members

Aparna Gudlur

Instructor

Biosketch:
I am a protein biochemist with a Ph.D. in structural biology from Centre for Cellular and Molecular Biology (CCMB), India and Masters (with distinction) in Biotechnology from M.S.U., India. Some noteworthy achievements include Cancer Research Institute (CRI) Irvington postdoctoral fellowship and Eli Lilly best graduate thesis award.

Research Focus:
My research revolves around understanding how the three-dimensional structure of a protein defines its cellular operations. In Prof. Hogan’s lab, I study how the calcium-sensor protein, STIM, and its partner, the calcium channel ORAI, transform from their respective resting states to an interacting calcium-conducting state that is responsible for calcium signaling in immune cells.

Career Goals:
I’m amazed by the complex functioning of STIM and ORAI, I aspire for an academic career focusing on the mechanism of action of these and other proteins of the calcium signaling pathway.

Xiaocui He

Postdoctoral Fellow

Biosketch:
I received my bachelor degree from Sun Yat-Sen University, China, in 2008, and my master degree in South China Sea Institute of Oceanology, Chinese Academy of Sciences, China, in 2011. After that, I proceeded to my PhD study in Friedrich Loeffler Institute, Germany and received the Ph.D. degree in 2014. Then I worked as a postdoctoral researcher in the Department of Molecular Immunology, Max-Planck-Institute of Immunobiology and Epigenetics, Germany from Feb. 2015 to Aug. 2017. Currently, I am a postdoctoral fellow in Dr. Patrick Hogan´s lab in La Jolla Institute for Allergy and Immunology.

Research Focus:
My research is mainly focusing on identification of interaction partners of NFAT that involve in controlling T cell tolerance. I also focus on the dynamic conformational changes of STIM1/ORAI and other key regulators in store-operated calcium entry during T cell activation. The ultimate goal of my research is to develop novel therapeutic strategies against autoimmune diseases and cancer.

Nupura Hirve

Research Technician III

Biosketch:
I graduated from San Diego State University with a masters degree in Cell and Molecular Biology in 2012. I began working as a Research Technician for Dr. Patrick Hogan in August 2012. My research focuses on calcium signaling in immune cells. Calcium plays an important role in proper functioning of the immune system. Two proteins, STIM and ORAI are responsible for maintaining steady levels of calcium inside the cells. Any defect in the function of these proteins can have detrimental effects on the immune system. The aim of my project is to investigate the molecular mechanism of STIM activation. I am probing how STIM changes its architecture from inactive to active state in response to calcium depletion. This study upon completion will enhance our understanding of the regulation of calcium ion levels in immune cells. Gaining control over this process will help us design better therapies for immunological disorders in humans.

Zachary Katz

Visiting Scientist

Giuliana Mognol

Postdoctoral Fellow

Biosketch:
I am a Molecular and Cellular Biologist, with a Master (2008) and a Ph.D. (2012) in Oncology from the Brazilian National Cancer Institute (INCA-RJ, Brazil). My research is focused on NFAT (nuclear factor of activated T cells) and IRF2BP2 (interferon regulatory factor 2 binding protein 2) proteins during cell cycle regulation, transformation and lymphocyte activation.

I moved to San Diego in 2012 to join Dr. Rao’s lab with a post-doc fellowship from CNPq-Brazil to construct transgenic mice for the IRF2BP2 gene. IRF2BP2 protein binds to NFAT and represses its transcriptional activity. In Rao’s lab I also investigated the molecular mechanisms of T cell exhaustion in cancer, where NFAT also has a pivotal role.

Currently, I work in Dr. Hogan’s lab, where I conducted a high-throughput screening to identify inhibitors of the NFAT-AP-1 interaction. The activation of NFAT in the absence of AP-1 (activation protein 1) is involved in T cell tolerance, while a productive immune response requires the physical interaction between NFAT and AP-1. A proper inhibitor of the NFAT-AP-1 interaction might find valuable applications to treat auto-immune and inflammatory diseases, where the productive arm of the immune response is exacerbate. We are now following up with some compounds identified in the high-throughput screening.

Career Goals:
I desire to follow up a career in scientific research focusing on the molecular and cellular mechanisms deregulated in autoimmune diseases and cancer, to improve the treatment of human diseases.

Emilie Tate

Intern

Shenghui Xue

Postdoctoral Fellow

Biosketch:
I obtained my bachelor’s degree in the field of biotechnology from the School of Life Science in Lanzhou University in 2005 and my Ph.D. degree from Department of Biology in Georgia State University in 2013. I worked as a postdoctoral researcher in the Department of Chemistry of Georgia State University from August 2013 to July 2015. I am currently a postdoctoral fellow in La Jolla Institute for Allergy and Immunology.

Research Focus:
My research is mainly focused on the oligomerization, gating and conformational changes of STIM1 and ORAI during calcium signaling at the molecular and cellular level using various computational, biochemical, and biophysical methods. Further understanding of the structural and molecular basis of STIM1, ORAI and other key regulators in store-operated calcium entry could aid in the design of novel therapeutic strategies against related diseases, such as autoimmune diseases and cancer. 

Ana Eliza Zeraik

Postdoctoral Fellow

Biosketch:
I received my Ph.D. in biophysics at the University of Sao Paulo (USP), Brazil, where I studied septins from the human pathogen Schistosoma mansoni, which causes the neglected disease schistosomiasis, endemic in developing countries. As a postdoctoral researcher, still at USP, I started working with the proteins STIM and ORAI from the same parasite, these proteins comprise the calcium release-activated (CRAC) channel. I joined Dr. Hogan’s lab to pursue the goal of understanding how S. mansoni STIM and ORAI function and the differences compared to the human CRAC channel. Finding the differences in the gating mechanism of calcium channels might be the first step to rational drug design, since calcium channels are potential targets to parasites.

Chen Zhang

Postdoctoral Fellow

Biosketch:
I received my Ph.D. in Biochemistry from Georgia State University, U.S. My research interests have been focused on calcium signaling in both physiological and pathological conditions. I have joined in Dr. Hogan’s lab to investigate how protein and lipid nanodomains influence the STIM-ORAI-mediated Ca2+-release-activated Ca2+ (CRAC) channel activation and Ca2+ influx. Using single-molecule imaging approaches I aim to identify the key lipid-domain rearrangements for STIM-ORAI-mediated Ca2+ signaling at the endoplasmic reticulum (ER)-plasma membrane (PM) junction and our ultimate goal is to understand how cellular Ca2+ signaling is central to activating the cells on the front lines of the battle against cancer.

Hogan Lab

Research Projects