Feng Qin PhD

Feng Qin

Feng Qin
PhD

Department of Physiology and Biophysics

Jacobs School of Medicine & Biomedical Sciences


Specialty/Research Focus

Ion channel kinetics and structure; Membrane Transport (Ion Transport); Molecular and Cellular Biology; Molecular Basis of Disease; Neurobiology; Pain Management; Protein Function and Structure; Signal Transduction

Contact Information
330 Cary Hall
Buffalo, NY 14214
Phone: (716) 829-6030
Fax: (716) 829-2569
qin@buffalo.edu



Professional Summary:

We study structural functions of ion channels involved in pain and temperature sensation. Nearly 1/3rd of the population suffers from some form of pain each year, yet less than 30% experience adequate relief with painkillers. Modern pain medications are not only ineffective, but also extremely outdated, with little to no progress having been made in the past 60 years. As a result, patients routinely turn to opioids for relief, spurring a culture of addiction and abuse in what is currently known as the opioid epidemic. The development of new painkillers is badly needed to combat this ongoing crisis. A promising drug target lies in a family of ion channels known as TRP (transient receptor potential) channels. These channels are located in sensory neurons of the peripheral nervous system and are responsible for registering pain-inducing stimuli.

TRP channels are sensitive to extreme temperatures. Unlike ligand- or voltage-dependent gating, the mechanism behind temperature activation is unknown. Our lab studies two subgroups of thermosensitive TRP channels including TRPV1, which is activated by extreme heat (>42°C) and TRPM8, which is activated by cold and menthol.

Most pain stems from tissue damage caused by physical injury or disease (i.e. cancer). Damaged tissues trigger the release of inflammatory markers and chemicals, which cause nociceptors to overreact, producing sensations of pain. TRP channels can interact directly, or indirectly with these compounds, contributing to these sensations. We are interested in how TRP channels detect and combine signals from different types of these compounds.

Capsaicin (hot ingredient in chili peppers) evokes an unpleasant burning sensation by activating TRPV1. Ironically, capsaicin is also used in topical creams as a way to relieve pain. The therapeutic benefits of capsaicin are believed to originate from its ability to switch the channel into a refractory or desensitized state. We are interested in the signaling pathway responsible for bringing about this functional desensitization as well as potential ways of exploiting it for pain relief.

We employ a variety of techniques spanning multiple disciplines including electrophysiology, molecular biology, biophysics, biochemistry and structural & computational biology. We study these ion channels both in vitro in living cells and in situ by purifying and inserting them into artificially made liposomes. We see these channels as miniature machines, with each part posing a distinct function. Our bread and butter consists of using patch clamp (which lets us monitor ion channel functioning) with mutagenesis to pinpoint the functional role behind each structural part. We are also using cryo-EM to visualize the different structural forms these channels adopt under different temperatures. We then map these distinct conformations to their respective functions by using luminescence energy transfer (LRET), an optical technique capable of discerning individual moving parts of the protein, in conjunction with molecular dynamics (MD) simulations. At the cellular level we are interested in the signaling cascade that regulates channel activity. An example of this is an experiment we performed where we used fluorescence microscopy (TIRF) in conjunction with patch clamp. TIRF microscopy allowed us to monitor fluctuating PIP2 levels within the plasma membrane whereas the patch clamp allowed us to monitor TRPV1 functionality. The experiment allowed us to observe a causal relationship, wherein a decrease in PIP2 concentration led to TRPV1 desensitization.

Our lab places a strong focus on building new tools. For example, we recently developed a fast temperature clamp using infrared laser diodes. This contraption permits ultra-fast local heating of single cells and has proven vital to our study of thermal channels. We also possess a custom-built microscopy-based LRET detection system (with a pulsed ND:YAG laser) for spectroscopic studies. We have also developed a suite of algorithms for interpreting data from single-channel recording, a type of measurement that supplies rich information regarding channel functioning. This software, known as QuB, is world-renowned and used by ion channel researchers worldwide. Students will not only have the opportunity to use state-of-the-art equipment to conduct cutting-edge biomedical research, but will also have the opportunity to gain deeper insight as to the technical aspects behind the tools they use.

Education and Training:

  • PhD, Biophysics, State University of New York at Buffalo (1996)
  • BS, Electrical Engineering, University of Science and Technology of China (1988)
  • BS, Mathematics, University of Science and Technology of China (1988)

Employment:

  • Associate Professor, Dept of Physiology and Biophysics, State University of New York at Buffalo (2005-present)
  • Assistant Professor, Dept of Physiology and Biophysics, State University of New York at Buffalo (1999–2005)
  • Research Assistant Professor, Dept of Physiology and Biophysics, State University of New York at Buffalo (1997–1999)
  • Post Doctoral Fellow, Department of Biophysical Sciences, State University of New York at Buffalo (1996–1997)
  • Research Assistant, Department of Biophysical Sciences, State University of New York at Buffalo (1992–1996)
  • Research Assistant, MRC Laboratory of Molecular Biology, United Kingdom (1992)

Awards and Honors:

  • Exceptional Scholar and Young Investigator Award, SUNY Buffalo (2004)
  • Top 100 Federal Grantee, SUNY Buffalo (2003)

Research Expertise:

  • Biochemistry & structural biology: Membrane protein expression, purification and reconstitution in artificial lipid bilayers, cryo-EM imaging and single-particle analysis
  • Calorimetry: Ultrasensitive DSC & ITC and quantitative modeling
  • Computational biology: Deep learning, artificial neuron network, hidden Markov modeling, maximum likelihood analysis, signal processing, image reconstruction
  • Electrophysiology: Patch-clamp (native cells & proteoliposomes), single-channel analysis
  • Laser heating: Ultrafast (sub-millisecond) temperature clamp in live cells, nanosecond T-jump
  • Microscopy & spectroscopy: TIRF microscopy, time-resolved spectroscopy, single-molecule imaging
  • Molecular biology

Grants and Sponsored Research:

  • March 2016–February 2019
    Temperature-Dependent Gating of Vanilloid Receptors (Award 74283)
    NIH
    Role: Principal Investigator
    $449,977
  • April 2013–February 2016
    Temperature-Dependent Gating of Vanilloid Receptors (Award 64563)
    NIH
    Role: Principal Investigator
    $1,021,754
  • June 2009–January 2014
    Algorithms for Molecular Kinetics (Award 50134)
    NIH
    Role: Principal Investigator
    $1,897,379
  • August 2007–May 2013
    Mechanisms of Heat Activation & Polymodal Gating of VR1 Receptor Channels (Award 43926)
    NIH
    Role: Principal Investigator
    $1,244,668
  • June 2010–May 2011
    ARRA: Mechanisms of Heat Activation and Multimodal Functions of VR1 Receptor Channels (Award 54780)
    NIH
    Role: Principal Investigator
    $75,000
  • April 2008–August 2010
    Laser Device for Ion Channel Activation (Award 46757)
    NIH
    Role: Co-Investigator
    $9,978
  • April 2005–March 2009
    Algorithms for Molecular Kinetics (Award 35937)
    NIH
    Role: Principal Investigator
    $1,529,531
  • June 2002–July 2007
    Structures & Mechanisms of Heat Activation & Polymodal Gating of VR1 Receptors (Award 25110)
    NIH
    Role: Principal Investigator
    $1,082,040
  • April 2000–March 2005
    Algorithms for molecular kinetics (Award 010284)
    NIH
    Role: Principal Investigator
    $1,975,782
  • April 1996–March 2000
    Algorithms for Molecular Kinetics (Award 001528)
    NIH
    Role: Principal Investigator
    $980,717

Journal Articles:

  • Liu B and Qin F. A single-residue molecular switch for high temperature dependence of vanilloid receptor TRPV3. Proc Natl Acad Sci USA. 2017.
  • Liu B and Qin F. Use Dependence of Heat Sensitivity of Vanilloid Receptor TRPV2. Biophys J. 2016; 110.
  • Wen H, Qin F and Zheng W. Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation. Protein. 2016; 84.
  • Liu B and Qin F. The Xenopus tropicalis orthologue of TRPV3 is heat sensitive. J Gen Physiol. 2015; 146.
  • Gregorio-Teruel L, Valente, P, Liu B, Fernández-Ballester G, Qin F and Ferrer-Montiel. The INTEGRITY OF THE TRP DOMAIN IS PIVOTAL FOR CORRECT TRPV1 CHANNEL GATING. Biophys J. 2015; 109.
  • Zheng W and Qin F. A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation. J Gen Physiol. 2015; 145.
  • Wu Y, YF Liu, PP Hou, ZH Yan, WJ Kong, BY Liu, X Li, J Yao, YX Zhang, F Qin, J Ding. Functionally Coupled with BK(mSlo1) Channels in Rat Dorsal Root Ganglion (DRG) Neurons. Plos One.. 2013.
  • Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. TRPV1 Channels Are Intrinsically Heat Sensitive and Negatively Regulated by Phosphoinositide Lipids. Neuron. 2013; 77.
  • Liu B, Yao J and Qin F. Hysteresis of gating underlines sensitization of TRPV3 channels. J Gen Physiol. 2011; 139.
  • Liu B, Yao J and Qin F. Modular thermal sensors in transient receptor potential (TRP) channels. Proc Natl Acad Sci USA. 2011.
  • Yao J, Liu B, Qin F. Kinetic and energetic analysis of thermally activated TRPV1 channels. Biophys J. 2010; 99(6).
  • Qin F. Hill coefficients of a polymodal Monod-Wyman-Changeux model for ion channel gating. Biophys J. 2010; 99(3).
  • Liu B, Yao J, Wang Y, Li H, Qin F. Proton inhibition of unitary currents of vanilloid receptors. J Gen Physiol. 2009; 134(3).
  • Yao J, Liu B, Qin F. Rapid temperature jump by infrared diode laser irradiation for patch-clamp studies. Biophys J. 2009; 96(9).
  • Yao J, Qin F. Interaction with phosphoinositides confers adaptation onto the TRPV1 pain receptor. PLoS Biol. 2009; 7(2).
  • Liu B, Qin F. Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J Neurosci. 2005; 25(7).
  • Liu B, Ma W, Ryu S, Qin F. Inhibitory modulation of distal C-terminal on protein kinase C-dependent phospho-regulation of rat TRPV1 receptors. J Physiol. 2004; 560(Pt 3).
  • Qin F, Li L. Model-based fitting of single-channel dwell-time distributions. Biophys J. 2004; 87(3).
  • Liu B, Hui K, Qin F. Thermodynamics of heat activation of single capsaicin ion channels VR1.. Biophys J. 2003; 85(5).
  • Ryu S, Liu B, Qin F. Low pH potentiates both capsaicin binding and channel gating of VR1 receptors.. J Gen Physiol. 2003; 122(1).
  • Qin F, Auerbach A, Sachs F. Hidden Markov modeling for single channel kinetics with filtering and correlated noise.. Biophys J. 2000; 79(4).
  • Qin F, Auerbach A, Sachs F. A direct optimization approach to hidden Markov modeling for single channel kinetics.. Biophys J. 2000; 79(4).
  • Qin F, Auerbach A, Sachs F. Maximum likelihood estimation of aggregated Markov processes.. Proc R Soc Lond B Biol Sci. 1997; 264(1380).
  • Qin F, Auerbach A. 1997; 109(2).
  • Qin F, Auerbach A, Sachs F. Estimating single-channel kinetic parameters from idealized patch-clamp data containing missed events.. Biophys J. 1996; 70(1).
  • Sachs F, Qin F. Gated, ion-selective channels observed with patch pipettes in the absence of membranes: novel properties of a gigaseal.. Biophys J. 1993; 65(3).
See all (16 more)

Books and Book Chapters:

  • Liu B and Qin F. Patch-Clamp Combined with Fast Temperature Jumps to Study Thermal TRP Channels. TRP Channels Methods and Protocols. 2019.
  • Leon Islas and Feng Qin. Thermal Sensors. 2015.
  • Qin F. Temperature Sensing by Thermal TRP Channels: Thermodynamic Basis and Molecular Insights. Thermal Sensors. 2015; 74.
  • Qin F. Time-resolved activation of thermal TRP Channels by fast temperature jumps. Methods in Signal Transduction Series. 2010.
  • Planells-Cases R, Valente P, Ferrer-Montiel A, Qin F, Szallasi A. Complex Regulation of TRPV1 and Related ThermoTRPs. Transient Receptor Potential Channels. 2010.
  • Qin F. Regulation of TRP ion channels by phosphatidylinositol-4,5-bisphosphate. Handb Exp Pharmacol. 2007; (179).
  • Qin F. Principles of single-channel kinetic analysis. Methods Mol Biol. 2007; 403.

Evaluative Studies and Case Reports:

  • Hui K, Liu B, Qin F. Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding.. Biophys J. 2003; 84(5).

Service Activities:

  • Jacobs School of Medicine & Biomedical Sciences Admissions Committee; Member (2019)

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Contact Information

330 Cary Hall
Buffalo, NY 14214
Phone: (716) 829-6030
Fax: (716) 829-2569
qin@buffalo.edu