Kenton J. Swartz, Ph.D.

Job Title
Senior Investigator, Molecular Physiology & Biophysics Section
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Kenton Swartz, Ph.D.
Division
Division of Intramural Research
Areas of Interest

Ion Channels, Transporters and Neurotransmitter Receptors

Contact
Contact Email
Contact Number

Dr. Swartz received his B.S. in Chemistry and Biology from Eastern Mennonite College in 1986. He received his Ph.D. in Neurobiology from Harvard University in 1993 where he worked with Bruce Bean studying the regulation of voltage-gated calcium channels by G-proteins and protein kinases. He did postdoctoral training with Roderick MacKinnon at Harvard Medical School, where he began isolating and studying toxins that interact with voltage-activated potassium channels.

Dr. Swartz joined NINDS as an Investigator in 1997 to establish a laboratory studying the structure and operational mechanisms of ion channel proteins. He was promoted to Senior Investigator in 2003, received the NIH Directors Award for Scientific Achievement in 2008 and the Kenneth S. Cole Award from the Biophysical Society in 2017. His laboratory is currently using biochemical, molecular biological, biophysical and structural techniques to investigate the structure and functional mechanisms of voltage-activated ion channels, TRP channels and P2X receptor channels.

Research Interests

The overarching goal of the Molecular Physiology and Biophysics Section is to elucidate how ion channel proteins sense critical biological stimuli, including membrane voltage, temperature, chemical ligands and mechanical forces. Each of these sensing mechanisms are intrinsic to ion channel proteins that play essential roles throughout biology and that are particularly important within the nervous system where their activity underlies every sensation, perception, thought and movement. The laboratory uses biochemical, molecular biological, electrophysiological and structural approaches to investigate the structure and functional mechanisms of voltage-activated ion channels, TRP channels, P2X receptor channels and mechanosensitive ion channels.

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Ion channel proteins as molecular sensors.

The research focus of the laboratory is to understand how ion channel proteins sense critical biological stimuli, including membrane voltage, temperature and chemical signals. Understanding the structure and mechanisms of voltage-activated ion channels is of fundamental importance because these proteins generate nerve impulses and thereby enable neurons to signal rapidly over long distances. A mechanistic understanding of these proteins is of medical significance because they are involved in many diseases, and are widely targeted by therapeutic drugs. X-ray structures of voltage-activated potassium (Kv) channels in activated/open states have led to new ideas about how interactions between voltage-sensing domains and the lipid membrane may be crucial for the function of these channels. We are exploring this theme using a range of approaches, including using tarantula toxins that bind to voltage-sensing domains within the membrane to investigate the protein-lipid interface and solve the structure of a resting/closed state. We have also discovered a new protein that contains an identifiable S1-S4 voltage-sensing domain and large cytoplasmic termini, which we named Coupled Voltage Sensor (CVS). Our results suggest that CVS is a functional voltage sensor, and we are currently testing the hypothesis that CVS interacts with intracellular signaling pathways.

We also study the mechanism by which transient receptor potential (TRP) channels sense changes in temperature, a mechanism that is critical for their biological roles in thermoregulation and detection of noxious stimuli. Studies with tarantula toxins and regulatory ion binding sites point to a critical role of the external pore in the gating mechanisms of TRPV1, and we are working to localize the temperature sensor and understand its mechanism. Our efforts to understand the structure and operational mechanisms of ligand-activated ion channels involved in intercellular communication has focused on P2X receptor channels, a family of trimeric cation channels that are activated by extracellular ATP. Thus far we have explored the structure and dynamics of the pore, and investigated whether the pore undergoes dilation in response to continual activation. We are currently exploring two distinct mechanisms by which divalent cations differentially regulate P2X receptors, either by binding along with ATP and determining the forms of ATP that serve as agonists, or by binding within an unusual chamber within the large extracellular domain to regulate the process of opening or desensitization.

If you are interested in joining the lab, send an email to Kenton Swartz describing your scientific background and why you are interested. Feel free to touch base with current or former lab members to ask any additional questions.

Lab Members

  • Nathan Bernhardt, Ph.D. - Staff Scientist
  • Tsg-Hui Chang, M.S. - Lab Manager
  • Matthew Denley, Ph.D. - Postdoctoral Fellow
  • Surbhi Dhingra, Ph.D. - Postdoctoral Fellow
  • Louis Tung Faat Lai, Ph.D. - Postdoctoral Fellow
  • Purushotham Selvakumar, Ph.D.  - Research Fellow
  • Xiaofeng Tan, Ph.D. - Research Fellow
  • Adrian Koretsky, B.S. - Postbaccalaureate Fellow
  • Hana Munshi, B.S. - Postbaccalaureate Fellow
  • Anabel Fernandez-Marino, Ph.D. - Special Volunteer
  • Katherine Huffer, A.B., Ph.D. - Special Volunteer
  • Magalí Colomer-Molera, M.S., B.S. - Graduate Student Intern
  • Giulia Dalaty, B.S. - Graduate Student, NIH/Karolinska Institute Partnership
  • Maia Moog, M.S., B.S. - Graduate Student, NIH/Karolinska Institute Partnership

 

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Group of lab members from the Swartz lab.

 

Lab Alumni

Former Predoctoral Members of the Lab:

Rosalind Chuang (1997-1999)
M.D., 2003, University of Washington School of Medicine, Seattle, WA
Present Position: Medical Director, Biogen, Cambridge, MA
LinkedIn Profile

Jeffrey Winterfield (1998-1999)
M.D., 2001, University of Chicago, Chicago, Il
Present Position: Associate Professor and Hank and Laurel Greer Chair in Cardiac Electrophysiology, Department of Medicine, Medical University of South Carolina, Charleston, SC
LinkedIn Profile

Gilberto Soler-Llavina (1999-2001)
PhD 2007 Program in Neuroscience, Harvard Medical School, Boston, MA
Present Position: Senior Principal Scientist, Novartis Institute for BioMedical Research, Boston, MA
LinkedIn Profile

Julia Wang (2001-2003)
MD, 2007, Case Western Reserve University School of Medicine, Cleveland, OH

Jan Vobecky (2003-2004)
MD, 2008, Vanderbilt University School of Medicine, Nashville, TN
Present Position: ER Physician, CEP America
LinkedIn Profile

AbdulRasheed Alabi (2005-2007)
MD, 2012, Stanford University School of Medicine, Stanford, CA
Present Position: Fellow in Cardivascular Diseases, Massachusetts General Hospital, Boston, MA
LinkedIn Profile

Margaret Yoder (2008-2010)
DO, 2014, Edward Via College of Osteopathic Medicine, Blacksburg, VA
Present Position: Family Medicine Physician
LinkedIn Profile

Kelsey Ladt (2009-2011)
MD/PhD student, University of California, San Diego, CA
Current Position: Resident, Child Neurology, University of California, San Diego

Sonya Hanson (2009-2013)
PhD, 2014, Oxford University, Oxford, United Kingdom
Present Position: Research Scientist, Center for Computational Biology, Flatiron Institute, New York City, NY
Sonya Hanson

Maryam Zamanian (2011-2013)
MD, 2017, University of Pittsburg School of Medicine, Pittsburg, PA
Present Position: Clinical Assistant Professor, University of Wisconsin
University Wisconsin Faculty Profile

Gabriel Heymann (2011-2013)
MD/PhD, 2020, University of Washington, Seattle, WA
Present Position: Resident, Internal Medicine, Yale-New Haven Hospital, New Haven, CT
Gabriel Heymann, MD/PhD  - Yale School of Medicine

Charise Garber (2012)
MD/PhD, 2020, Washington University School of Medicine, St. Louis, MO
Present Position: Resident, Neurosurgery, Washington University School of Medicine, St. Louis, MO
Charise Garber, MD, PhD - Neurosurgery

Erika Babikow (2013-2014)   
DMD, 2020, University of Pittsburg School of Dentistry, Pittsburg, PA
Present Position: Resident, Orthodontics, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC
Erika Babikow - Adams School of Dentistry : Adams School of Dentistry

Emily Harnish (2013-2015)     
PA, 2020, James Madison University, Harrisonburg, VA
Present Position: Physician Assistant, Penn State Health
LinkedIn Profile

Benjamin George (2016-2019)  (Postbaccaulareate Fellow)
Present Position: Graduate Student, Department of Biology, Carnegie Mellon University, Pittsburg, PA
LinkedIn Profile

Aaron Gochman (2017-2019)
Present Position: MD/PhD Student, Vanderbilt University School of Medicine, Nashville, TN
LinkedIn Profile

Stephanie Tam (2019-2022)
Present Position: Graduate Student, Molecular Biophysics Training Program, Weill Cornell Medicine and Sloan Kettering, New York, NY

Charlotte Godfrey (2021-2023)
Present Position: Graduate Student, Yale University School of Medicine, New Haven, CT     

Elisabeth Oskoui (2021-2023)
Present Position: Undergraduate, Imperial College London, London, UK

William Khayyo (2022-2024)
Present Position: Graduate Student, Molecular Biophysics Training Program, Weill Cornell Medicine and Sloan Kettering, New York, NY

Former Postdoctoral Members of the Lab:

David Hackos (1998-2001)
PhD, 1998, University of California, San Francisco, CA
Present Position: Senior Principal Scientist, Neuroscience, Genentech, San Francisco, CA
Genentech: David Hackos | Senior Principal Scientist, Neuroscience

Yingying Li-Smerin (1997-2003)
PhD, 1997, University of Pittsburg, Pittsburg, PA
Present Position: Scientific Review Officer, NHLBI, NIH

Hwa Lee (2002-2004)
PhD, 2002, University of Virginia, Charlottesville, VA
Present Position: Senior Intellectual Property Attorney, Intuitive, San Diego, CA
LinkedIn Profile

Tetsuya Kitaguchi (2001-2005)
PhD, 2001, Kyoto University, Kyoto, Japan
Present Position: Associate Professor, Tokyo Institute of Technology, Japan
Technologies for observing and manipulating cells - kitaguchi page!

Shai Silberberg (2002-2005)  
On sabbatical while am Associate Professor, Ben Gurion University, Israel
Present Position: Director of Research Quality, NINDS, NIH, Bethesda, MD
Shai Silberberg | National Institute of Neurological Disorders and Stroke (nih.gov)

Ashok Ramalingam (2003-2005)
PhD, 2001, National University of Singapore, Republic of Singapore
Present Position: Executive, Advanced Clinical Analytics, United States Department of Defense, Fairfax, VA
LinkedIn Profile

Manana Sukhareva (2001-2005)
PhD, 1987, Institute of Electrochemistry of Academy of Sciences, Moscow USSR
Present Position: Director, Office of Scientific Review, NIBIB, NIH, Bethesda, MD
Manana V Sukhareva | National Institute of Biomedical Imaging and Bioengineering

L. Revell Phillips (2004-2008)
PhD, 2003, Washington University School of Medicine, St. Louis, MO
Present Position: Science and Technology Manager, Defense Threat Reduction Agency, Department of Defense, Fort Belvoir, VA
LinkedIn Profile

Maria Isabel Bahamonde Santos (2005-2009)
PhD, 2003, Pompeu Fabra University, Barcelona, Spain
Present Position: Researcher, Electrophysiology Facility, University Hospital Zurich, Zurich, Switzerland
LinkedIn Profile

Mirela Milescu (2004-2011)
PhD, 2004, State University of New York, Buffalo, NY
Present Position: Scientific Review Officer, NINDS, NIH
LinkedIn Profile

Mufeng Li (2005-2021)
PhD, 2005, Neurobiology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, P.R. China
Present Position: Scientific Review Officer, Center for Science Review, NIH
Dr. Mufeng Li | NIH Center for Scientific Review

Dmitriy Krepkiy (2006-2015)
PhD, 2002, University of Wisconsin, Milwaukee, WI
Present Position: Program Director, Biomedical Technology Branch
Division of Biomedical Technology, Bioinformatics and Computational Biology, NIGMS
Biographical Sketch: Dmitriy Krepkiy, Ph.D.

Frank Bosmans (2006-2012)
PhD, 2005, Catholic University of Leuven, Leuven, Belgium
Present Position: Professor, Department of Basic and Applied Medical Sciences, Ghent University, Belgium
Molecular Physiology and Neurophysics Group — Department of Basic and Applied Medical Sciences — Ghent University

Jaime Smith (2007-2012)
PhD, 2006, Biochemistry, State University of New York, Buffalo, NY
Present Position: Health Science Policy Analyst, NIDDK, NIH
LinkedIn Profile

Jeet Kalia (2008-2013)
PhD, 2008, Biochemistry, University of Wisconsin, Madison, WI
Present Position: Associate Professor, Indian Institute of Science Education and Research, Bhopal, India
Ion channels, Lipids, Bioconjugation.

Toshi Kawate (2009-2011)
PhD, 2005, Columbia University, New York, NY
Present Position: Associate Professor, Department of Molecular Medicine, Cornell University College of Veterinary Medicine, Ithaca, NY
Toshi Kawate, PhD | Cornell University College of Veterinary Medicine

Renee Martin (2012-2013)
PhD, 2011, Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia, PA 
Present Position: Director of Global Regulatory Affairs, Amgen
LinkedIn Profile

Ferenc Papp (2012-2014)
PhD, 2010, Membrane Biophysics, Molecular Medicine, Debrecen, Hungary
Present Position: Assist. Professor, Department of Membrane Biophysics, University of Debrecen, Hungary
Ferenc Papp | Department of Biophysics and Cell Biology

Feng Zhang (2012-2017)
PhD, 2011, Neuroscience, Peking University, Beijing, China
Present Position: Postdoctoral Fellow, Department of Biochemistry, Duke University School of Medicine, Durham, NC
Lab Members | Lee Lab

Orsolya Szilagyi (2014-2019)
PhD, 2014, Membrane Biophysics, University of Debrecen, Debrecen, Hungary
Present Position: European Product Manager, Microscopy, Nikon Instruments, Amsterdam, Netherlands
LinkedIn Profile

Suvendu Lomash (2014-2020)
PhD, 2009, National Institute of Immunology, New Delhi, India
Present Position: Senior Scientist III, NextCure, Baltimore, MD
LinkedIn Profile

Andrés Jara-Oseguera, (2012-2021)
PhD, 2012, Biomedical Sciences, Universidad Nacional Autonoma de Mexico, Mexico
Present Position: Assistant Professor, Dept. Molecular Biosciences, UT Austin
Jara-Oseguera, Andrés - Molecular Biosciences - CNS Directory

Chanhyung Bae (2013-2021)
PhD, 2012, Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju, Korea
Present Position: Senior Scientist, Janssen Research and Development, Philadelphia, PA

Kanchan Gupta (2013-2021)
PhD, 2012, National Institute of Immunology, Jawaharlal Nehru Univ., India
Present Position: Senior Scientist, Rubius Theraputics, Cambridge, MA
LinkedIn Profile

Gil Toombes (2012-2022)
PhD, 2007, Physics, Cornell University, Ithaca, NY

Angela Ballesteros Morcillo  (2015-2022)
PhD, 2012, Molecular Biology, Autonoma University Madrid, Spain
Present Position: Stadtman Tenure-Track Investigator, NIDCD, NIH
LinkedIn Profile

Xiaosa Wu (2020-2022)
PhD, Present Position: Postdoctoral Research Fellow, School of Biomedical Sciences, the University of Queensland, Queensland, Australia

Anabel Fernández-Mariño  (2017-2024)
PhD, 2013, University Pompeu Fabra, Barcelona, Spain
Present Position: Assistant Professor, Department of Physiology and Biophysics, University of Colorado, Anschutz Medical Campus, Aurora, CO
UCD Anschutz Faculty Profile

 

Selected Publications

Publications
1.Tan XF, Fernández-Mariño AI, Li Y, Chang T-H and Swartz KJ. (2025) Structural basis of fast N-type inactivation in Kv channels. Nature (in press).
2.Conservation of the cooling agent binding pocket within the TRPM subfamily.
Huffer Kate, Denley Matthew CS, Oskoui Elisabeth V, Swartz Kenton J (2024) 
ELife 13:RP99643.
3.Dilation of ion selectivity filters in cation channels. 
Huffer K, Tan XF, Fernández-Mariño AI, Dhingra S, Swartz KJ. 
Trends Biochem Sci. 2024 May;49(5):417-430. doi: 10.1016/j.tibs.2024.02.004. Epub 2024 Mar 20.
PMID: 38514273 Free PMC article.
4.Inactivation of the Kv2.1 channel through electromechanical coupling.
Fernández-Mariño AI, Tan XF, Bae C, Huffer K, Jiang J, Swartz KJ.
Nature. 2023 Oct;622(7982):410-417. doi: 10.1038/s41586-023-06582-8. Epub 2023 Sep 27.
PMID: 37758949 Free PMC article.
5.Regulation of membrane homeostasis by TMC1 mechanoelectrical transduction channels is essential for hearing.
Ballesteros A, Swartz KJ.
Sci Adv. 2022 Aug 5;8(31):eabm5550. doi: 10.1126/sciadv.abm5550. Epub 2022 Aug 3.
PMID: 35921424 Free PMC article.
6.Structures of the T cell potassium channel Kv1.3 with immunoglobulin modulators.
Selvakumar P, Fernández-Mariño AI, Khanra N, He C, Paquette AJ, Wang B, Huang R, Smider VV, Rice WJ, Swartz KJ, Meyerson JR.
Nat Commun. 2022 Jul 4;13(1):3854. doi: 10.1038/s41467-022-31285-5.
PMID: 35788586 Free PMC article.
7.Structure of the Shaker Kv channel and mechanism of slow C-type inactivation.
Tan XF, Bae C, Stix R, Fernández-Mariño AI, Huffer K, Chang TH, Jiang J, Faraldo-Gómez JD, Swartz KJ.
Sci Adv. 2022 Mar 18;8(11):eabm7814. doi: 10.1126/sciadv.abm7814. Epub 2022 Mar 18.
PMID: 35302848 Free PMC article.
8.Global alignment and assessment of TRP channel transmembrane domain structures to explore functional mechanisms.
Huffer KE, Aleksandrova AA, Jara-Oseguera A, Forrest LR, Swartz KJ.
Elife. 2020 Aug 17;9:e58660. doi: 10.7554/eLife.58660.
PMID: 32804077 Free PMC article.
9.The ion selectivity filter is not an activation gate in TRPV1-3 channels.
Jara-Oseguera A, Huffer KE, Swartz KJ.
Elife. 2019 Nov 14;8:e51212. doi: 10.7554/eLife.51212.
PMID: 31724952 Free PMC article.
10.Molecular mechanisms of human P2X3 receptor channel activation and modulation by divalent cation bound ATP.
Li M, Wang Y, Banerjee R, Marinelli F, Silberberg S, Faraldo-Gómez JD, Hattori M, Swartz KJ.
Elife. 2019 Jun 24;8:e47060. doi: 10.7554/eLife.47060.
PMID: 31232692 Free PMC article.
11.Conserved allosteric pathways for activation of TRPV3 revealed through engineering vanilloid-sensitivity.
Zhang F, Swartz KJ, Jara-Oseguera A.
Elife. 2019 Jan 15;8:e42756. doi: 10.7554/eLife.42756.
PMID: 30644819 Free PMC article.
12.Structural relationship between the putative hair cell mechanotransduction channel TMC1 and TMEM16 proteins.
Ballesteros A, Fenollar-Ferrer C, Swartz KJ.
Elife. 2018 Jul 31;7:e38433. doi: 10.7554/eLife.38433.
PMID: 30063209 Free PMC article.
13.Lipids surf the groove in scramblases.
Ballesteros A, Swartz KJ.
Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):7648-7650. doi: 10.1073/pnas.1809472115. Epub 2018 Jul 6.
PMID: 29980647 Free PMC article. No abstract available.
14.TRPM channels come into focus.
Bae C, Jara-Oseguera A, Swartz KJ.
Science. 2018 Jan 12;359(6372):160-161. 
doi: 10.1126/science.aar6205.
PMID: 29326261 No abstract available.
15.Heat activation is intrinsic to the pore domain of TRPV1.
Zhang F, Jara-Oseguera A, Chang TH, Bae C, Hanson SM, Swartz KJ.
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):E317-E324. doi: 10.1073/pnas.1717192115. Epub 2017 Dec 26.
PMID: 29279388 Free PMC article.
16.STRUCTURAL BIOLOGY. Twists and turns in gating ion channels with voltage.
Toombes GE, Swartz KJ.
Science. 2016 Aug 12;353(6300):646-7. doi: 10.1126/science.aah4194.
PMID: 27516583 No abstract available.

Complete publication list on PubMed.