Fellowship Mentors
John Bougther, Jr., PhD
Research Interest: Ingestive decisions play a key role in a number of human conditions
including obesity, diabetes, anorexia, hypertension, and coronary artery disease.
My lab uses neuroanatomical, neurophysiological, imaging and behavioral approaches
towards the study of ingestive behaviors in laboratory mice.
Another long-running interest in our lab is the study of the genetic underpinnings of oromotor function, especially fluid licking, in mice. We have conducted surveys of licking and ingestive microstructure with large panels of inbred and BXD recombinant inbred mice, and have identified loci on Chr 1 and 10 with major effects on lick rate (Boughter et al., 2012; St. John et al., 2017). Finally, I also collaborate with Faculty and Residents in the Department of Otolaryngology - Head and Neck Surgery, with recent projects using either animal models or human tissue.
Jianyang Du, PhD
Research Interest: Protons have been a proposed neurotransmitter for decades. Yet
only recently has solid evidence emerged to support this claim (Du J et al., 2014;
Highstein SM et al., 2014). Extracellular protons in the brain are an important signaling
messenger involved in neuronal functions. More importantly, numerous neurological
diseases such as ischemia, seizure, multiple sclerosis and neurodegenerative diseases
all generate acidosis. Understanding how protons signal not only helps us to better
understand neuronal physiology but also has important implications in their roles
in diseases. Acid-sensing ion channels (ASICs) are proton receptors. Their localization
and pH sensitivity put them in an ideal position to sense small pH changes at the
synaptic cleft and elsewhere in the neuron. ASICs are important in multiple aspects
of peripheral and central neuronal functions. ASICs have been implicated in aspects
of behavior and memory including fear-related learning and memory.
The long-term goal of my lab is to understand how protons regulate brain circuits and behaviors. Ultimately, this focus will lead to the development of novel therapeutic targets for treating emotional disorders such as anxiety, depression, post-traumatic stress disorder (PTSD) and schizophrenia. We believe that our current and future work will significantly impact the field of neuroscience by addressing the following important questions:
1. How do protons function as a neurotransmitter to control synaptic transmission in the brain? Addressing this question in a multidisciplinary fashion will significantly contribute to the understanding of the how neurotransmission occurs and is modified by protons.
2. How do protons amend and reshape neural circuits? How does this affect subsequent behavior(s)? One of the fundamental questions in neuroscience is how do neural circuits drive and modify behaviors. Illuminating how protons regulate neural circuits will provide insight into this complex and challenging area.
3. Can protons and their receptors function as a new therapeutic target for the treatment of neurological illnesses? The major proton receptors, ASICs have been suggested as targets for many neuronal diseases, including anxiety, depression, seizure, stroke and Parkinson’s disease, etc.. Developing therapeutics targeting proton signaling may therefore significantly benefit many individuals and improve the quality of life for hundreds of thousands of people. One of our ongoing projects, Acid-sensing ion channel 1a contributes to synaptic transmission and plasticity in ischemia, has been funded by American Heart Association.
Max Fletcher, PhD
Research Interest: My research focuses on understanding the basic principles of neural
encoding of sensory information and how both experience and learning can affect this
process. Specifically, my work has focused on investigating how simple forms of learning
can enhance sensory processing in the early stages of the olfactory pathway and lead
to changes in perception. To accomplish this, I have employed a broad range of techniques
including in vivo electrophysiology, awake and anesthetized in vivo imaging, in vivo
two-photon calcium imaging, and as well as behavioral approaches.
Kristin Hamre, PhD
Research Interest: Depending upon the interest of the student, there are two possible
types of techniques that a student could learn. One is that the student could learn
about behavioral testing of mice to examine both baseline and alcohol-mediated behaviors
that measure such parameters as anxiety and balance/ coordination. Second, through
the analysis of development a student could learn techniques such as genotyping through
the use of PCR and histological processing of tissue.
Tauheed Ishrat, PhD
Research Interest: The broad goal of our lab is to understand, at a cellular and molecular
level, the interplay between inflammation and oxidative stress in neurovascular injury
after stroke, and to develop novel therapeutic strategies. We integrate cellular,
molecular, genetic, and pharmacological approaches to elucidate the mechanisms that
control the progression of neurovascular brain injury after stroke.
Stroke is a major cause of long-term disability worldwide and there is no treatment for it except recombinant tissue type plasminogen activator (rtPA). rtPA can be administered only within a short time window (4.5 hours) after stroke onset, and it often leads to rupturing of the cerebrovascular system, leading to hemorrhage, oxidative stress and inflammation. We believe that treatment of acute stroke with rtPA in combination with certain potent neuroprotectants/ small molecules can combat oxidative stress and inflammation and will prove to be a good strategy to prevent secondary injury.
Our laboratory uses a multidisciplinary approach to examine the molecular mechanisms and therapeutic targets involving in neurovascular injury including, Western blotting, PCR, immunocytochemistry, and cutting edge neuroscience techniques. In addition, we incorporate a broad variety of functional behavioral tests useful for investigating experimental manipulations including, the Morris water maze, Beam walk open field apparatus, passive avoidance, CatWalk, rotarod apparatus, and Grip strength test, Novel Object recognition.
Megan Mulligan, PhD
Research Interest: The goal of my research is to use a holistic systems approach,
including genetic models, new molecular biology tools, and diverse bioinformatics
resources in order to identify mechanisms by which genetic and environmental variation
influence DNA modification, gene and protein expression, and neuronal function to
modulate complex behavior and disease states.
Developing a Reduced Complexity Cross for Efficient Behavioral Genetics. There are 40 to 50 million validated reference SNPs for human and mouse. This level of genomic complexity poses genuine challenges for the identification of polymorphisms that control trait variation and for modeling complex gene-gene and gene-environment interactions. To facilitate identification of candidate genes and variants that underlie behavior, I developed a reduced complexity cross (RCC) with low levels of genetic diversity but moderate to high levels of phenotypic diversity by crossing B6J and C57BL/6NJ (B6NJ) substrains. Separation and maintenance of inbred mouse colonies at different institutions lead to genetic drift over time and the creation of non-isogenic subpopulations. These substrain colonies are a valuable resource for studying the impact of naturally occurring mutations on complex traits. For example, the parental B6J and B6NJ mice used to generate my RCC F2 progeny have been separated and maintained at different breeding facilities since 1951. Despite a similar genetic background, these substrains demonstrate marked differences in addiction, metabolic, and behavioral traits.
Dissecting the Role of Genetic Variants in the GABA-A Receptor Alpha 2 Subunit (Gabra2). Genetic variation at the GABRA2 locus is associated with alcohol dependence, early life stress and addiction susceptibility, impulsivty, and differences in brain activity. I am using a combination of mouse models (knockout, CRISPR gene editing, and naturally occuring mutations) to evaluate the effects of variation in Gabra2 levels with the goal of better understanding the consequences of GABRA2 variation in human populations.
Stress and the Genome. Early life stress, chronic stress, and even acute exposure to stress are highly comorbid with a variety of physical and mental health outcomes in human populations. The exact genetic and epigenetic mechanisms driving these relationships are not well understood. I use different genetic mouse populations to identify gene variants that control stress reactivity and mediate alterations in alcohol consumption in response to stress and to identify common molecular pathways mediating stress induced alcohol consumption. Overarching goals are to identify individuals, based on genotype, that predict negative outcomes after stress exposure.
Lawrence T. Reiter, PhD
Research Interest: My laboratory utilizes the powerful genetic model organism Drosophila
melanogaster (fruit flies) to investigate the functions of genes involved in human
neurological diseases. Our main focus is the study of genes related to Angelman syndrome
and autism spectrum disorders. These disorders are interrelated at the molecular level
and one of the goals of our laboratory is to identify genes and proteins regulated
by one or more of the proteins that can cause and autism phenotype. In addition, approximately
3-5 % of all autism cases result from maternally derived duplications of the region
containing the gene that causes AS, UBE3A. Mutations in the protein targets of the
ubiquitin ligase UBE3A may therefore account for a significant percentage of idiopathic
autism cases as well.
In our laboratory we utilize Drosophila specific genetic techniques that allow us to generate artificially high levels of normal and mutant fly Dube3a proteins in fly heads. Wild type, dominant negative and epitope tagged forms of ube3a are over-expressed in the brains of flies using the GAL4/UAS system in order to increase or decrease the levels of Dube3a protein targets. We have now identified 50 of these potential Dube3a regulated proteins (Jensen et al. PLoS One. 2013 Apr 23;8(4):e61952) and are actively validating these interactions using whole genome molecular methods (genomics), genetic suppressor/enhancer screens, immunostaining in fly neurons (immunoflourescence), and changes in synaptic function and stability at the fly neuromuscular junction (electrophysiology). Using these methodologies in flies we have identified Dube3a regulation of the actin cytoskeleton (Reiter et al. Hum Mol Genet. 2006 Sep 15;15(18):2825-35) as well as the synthesis of monoamines (Ferdousy et al. Neurobiol Dis. 2011 Mar;41(3):669-77) and ion transport across axonal membranes (Jensen et al. PLoS One. 2013 Apr 23;8(4):e61952).
We have also been doing in depth phenotypic and molecular analysis of individuals with interstitial duplication 15q autism. Since 2007 we have been collecting a variety of language, neuropsychiatric, neurological and gene expression data from subjects with interstitial 15q chromosomal duplications and just recently published our clinical findings (Urraca et al. 2013 Autism Res. 2013 Aug;6(4):268-79). We hope that our basic research into the functional targets of UBE3A will lead to a better understanding of the phenotypes in this particular autism population where the UBE3A gene is duplicated, and presumably expressed at higher levels than in unaffected individuals. For more information on our clinical study see http://www.dup15q.org/events/scientific-conferences/2015-scientific-meeting/larry-reiter-2015/. As an extension of this work which bridges the gap between basic and clinical research, we recently began an NIH funded study to generate dental pulp derived neurons from individuals with either the Angelman syndrome deletion in this region or a duplication of this region on chromosome 15q causing autism. We hope that these patient-derive neuronal cultures will allow us to perform more in depth molecular and electrophysiological analysis of both conditions in the near future. For more information on the dental pulp stem cell study please see http://tinyurl.com/88f688l.
Research Interest: Mechanisms that regulate photoreceptor outer segment assembly; mouse models of eye disease; proteomics; retinal cell biology; mutagenesis; genetics modulators of glaucoma
Shalini Narayana, PhD
Research Interest: My research is centered on two main areas: 1. Optimizing the clinical application of non-invasive brain imaging and stimulation methods in diagnostic and therapeutic domains, and 2. Characterizing functional characterization of the speech and limb motor networks and disease, injury, and treatment induced plasticity in these systems. These research objectives are focused around human speech and motor systems and use multimodal neurophysiological imaging methods. The neuroimaging methods used include magnetoencephalography (MEG), Transcranial magnetic stimulation (TMS), and functional magnetic resonance imaging (fMRI).
Ongoing research projects include examining the therapeutic effects of TMS in speech and voice disorders in Parkinson's disease, and epilepsy. Other studies include developing population normative data of TMS derived neurophysiological parameters and optimizing non-invasive brain stimulation and functional imaging in the context of presurgical mapping.
The lab is also investigating functional connectivity of speech and limb motor systems. Studies are also characterizing changes in the speech motor system resulting from Parkinson's disease and the compensatory adaptations in the network following voice treatment as well as identifying neurophysiological correlates of performance enhancement resulting from motor training and adjuvant TMS.
Research interest: The research in our laboratory is primarily dedicated to a better understanding of neuroinflammatory processes following brain insults such as prolonged seizures. We have also recently begun to explore the neuron-glia interactions in malignant gliomas, the most devastating brain tumors that constitute a major cause for epilepsy, particularly in the elderly. We attempt to unlock the cellular and molecular mechanisms whereby normal brains are transformed to generate spontaneous recurrent seizures, i.e., acquired epileptogenesis. We are also interested in developing novel antiepileptic and/or antiepileptogenic therapeutics in close collaboration with medicinal chemistry laboratories. To achieve these goals, we use a variety of technologies and experimental systems, such as high-throughput screening, chemical genetics, TR-FRET, RNAi, CRISPR/Cas9, microdialysis, time-locked video EEG, behavioral tests, etc.
Research Interest: The major line of interest in the lab is the lipid regulation of alcohol effect on cerebral circulation at different points during lifetime (from in utero into late adulthood). We are currently pursuing several lines. We are studying the role of dietary cholesterol in the physiology and pathology of cerebral arteries via ion channel involvement. Using rat model of high-cholesterol diet, we were the first to show that dietary cholesterol was a critical nutritional regulator of alcohol-induced constriction of cerebral arteries. After establishing the phenomenon at organ level, we are currently dissecting out molecular and structural mechanisms that enable cholesterol regulation of alcohol-induced constriction of cerebral arteries. Considering that statins - cholesterol lowering therapy - are one of the most widely prescribed and consumed drugs, we are studying their effect on cholesterol level in cerebral artery tissue and on artery response to alcohol.
Another line of work is carried out in close collaboration with the Department of Comparative Medicine and with the Department of Obstetrics and Gynecology at UTHSC. This line of work involves non-human primates - baboons, whose pregnancy and developmental milestones are similar to humans. We are focused on the role of endocannabinoid lipids in alcohol effect on fetal cerebral circulation during maternal binge drinking. We are aiming at identification of novel targets of maternal drinking in fetal cerebral arteries. This exploratory work may lay a foundation to early diagnostics and successful prevention/treatment of the fetal alcohol spectrum disorders (FASD) and fetal alcohol syndrome (FAS) that are estimated to affect at least 1% of births in the USA.
In addition, we are working on the interaction of potassium (e.g. GIRK, BK) channels with physiologically relevant lipids. In close collaboration with Dr. Alex Dopico (UTHSC), we were able to map several lipid-sensing sites in both BK channel-forming and accessory beta 1 subunits. These studies include recognition motifs for bile acids, cholesterol, and leukotriene B4. We are currently working on developing synthetic ligands for these sites. Newly discovered ligands will be used as lead compounds for designing drugs that modulate diameter of cerebral arteries via action on BK channel. In another collaborative line with Dr. Avia Rosenhouse-Dantsker at the University of Illinois at Chicago we are studying molecular mechanisms of cholesterol modulation of GIRK channels and potential implications of such modulation on GIRK channel physiology and role in Down syndrome pathology.
Hao Chen, PhD
Research Interest: My long-term interest is to elucidate the complex interaction between
social, genetic, and sensory factors in regulating drug abuse behavior, particularly
cigarette smoking and alcohol drinking, by using rodent models. Behavioral, anatomical,
molecular, genetic, genomic and informatics approaches are integrated to investigate
the mechanisms underlying the effects of social and genetic factors on drug abuse
and addiction behavior.
Alex Dopico, MD, PhD
Research Interest: My laboratory is interested in determining the mechanism of action
of small amphiphilic compounds on ion channels from excitable cells. One of these
amphiphiles is alcohol, the most widely used and abused drug. Some others are physiological
modulators, such as bile acids and neurosteroids. Our current research is focused
on two projects dealing with large conductance, Ca++-activated K+ (BK) channels. These
channel proteins have been demonstrated to be involved in both controlling central
neuron excitability and regulating arterial smooth muscle tone. Project 1: To determine
the molecular basis for differential actions of alcohol on BK channels from mammalian
brain vs. arterial smooth muscle, including modulation of drug action by membrane
lipids. Project 2: To determine the structural requirements (both in the amphiphile
molecule and the ion channel protein) for the modulation of arterial muscle BK channels
by bile acids.
For these studies we combine electrophysiological and molecular biology techniques. Ion channel responses to drug exposure are evaluated in: 1) freshly isolated cells, where we study drug modification of channel behavior in the native environment of the channel protein; 2) isolated patches of cell membrane, where we can address the differential role of different membrane-bound vs. cytosolic second messengers in drug action; 3) artificial bilayers of controlled lipid composition, where we can determine the modulatory role of membrane lipids in drug action.
Ion channel isoforms from relevant tissue are identified. Following mRNA isolation and cloning, channel subunits of known sequence are expressed in heterologous systems such as Xenopus oocytes or HEK-293 cells. Then, we can determine the role of channel subunit composition in drug action by studying drug effects on ion channel complexes that differ in pore-forming and/or modulatory subunit composition. In addition, differential responses to a drug by channels that differ in a given region of a subunit, when studied in the same proteolipid environment, allow us to postulate sites in that subunit for drug recognition. This is probed by studying drug action on expressed channel proteins that include mutations in the postulated region(s).
My laboratory is interested in determining the molecular mechanism of action of alcohol and other small amphiphiles on ion channel proteins from the brain and arterial vessels. To determine the recognition sites for alcohol in these proteins and how alcohol modifies protein function upon interaction with these sites, will provide critical information for understanding how the drug interacts with its targets and, eventually, lead to the design of clinically useful agents to treat conditions associated with alcohol intake.
Chang Hoon Jee, PhD
Research Interest: My primary interest is synaptic plasticity associated with the
progress of Substance Use Disorder (SUD). Understanding underlying mechanism of SUD
offers extraordinary opportunities for the development of therapeutic treatments of
SUD.
Many SUD patients wish to stop abusing but fail in their attempt, even when effective cessation interventions are available. The compulsive seeking and taking despite the harmful consequences have been considered to explain this feature but underlying mechanism yet to be elusive. The compulsive seeking is characterized by an imbalance between the superior drive to substance and disruption in control of substance use. In order to model this highly complex neuromodulation, we addressed sophisticated behavioral paradigms in C. elegans, that have a simple nervous system but the most completely defined connectome, with the advantage of the straightforward genetic, behavioral, and neurophysiological investigation. We investigate molecular mechanism associated with compulsive alcohol/nicotine seeking behavior with genetic manipulations, microsurgeries, cell-type specific electrophysiological recordings, and optogenetic tool from Worms to Rodent models.
Kafait U. Malik, PhD, DSc
Research Interest: The overall objective of our research is to elucidate the cellular
and molecular signal transduction mechanisms of growth factors, circulating hormones
including angiotensin II (Ang II) and locally generated autacoids (eicosanoids) and
adrenergic transmitter norepinephrine (NE) in the regulation of cardiovascular function
in health and in the development of hypertension and vasculopathy associated with
restenosis, atherosclerosis and diabetes. Our studies should further our knowledge
of the neuro-humoral mechanisms that regulate vascular function and its alteration
in vascular diseases. Moreover, these studies should allow formulating rational approaches
for the development of novel therapeutic agents for the treatment of hypertension,
arteriosclerosis and restenosis.
We use isolated cultured vascular smooth muscle and endothelial cells, isolated perfused organs (heart, kidney and blood vessels), wire myograph for measuring vascular reactivity models of hypertension (Ang II- and DOCA-Salt and SHR), balloon injured carotid artery and now we are also transgenic animals for our studies. The laboratory techniques also include the use of HPLC-GC-Mass spectrometric Analysis of Eicosanoids, SDA-PAGE and Western blot analysis, DNA and RNA isolation, purification and quantitation, PCR, RT-PCR, Q-PCR, DNA transfection in cells Plasmid preparation, restriction fragment mapping, Construction of siRNA of various signal molecules, Transfection of reporter vectors as well as over-expression of constitutively active or dominant negative proteins, Co-immunoprecipitation and co-localization techniques, con-focal microscopy, site direct mutagenesis Molecular imaging of protein interactions Immunoassays and protein analysis, insertion of miRNA into adeno-, lenti- and adeno-associated viral vectors and preparation of viruses for transfection in cultured cells and for in vivo use. The signaling molecules studied by ELISA, in vitro kinase assay and Proteomics include, RasGTPas, ERK1/2, MEK, Raf, p38MAPK, c-JNK, PI3 kinase, Akt, JAK-STA, Pyk-2, c-Src, Syk and EGF.
Kazuko Sakata, PhD
Research Interest: Current projects in my laboratory focus on studying the roles of
gene regulation of brain-derived neurotrophic factor (BDNF) in major depression. BDNF
is a major neuronal growth factor in the brain that promotes neuronal development
and synaptic plasticity. BDNF has been suggested to be involved in both pathophysiology
of depression and action of antidepressants; BDNF expression is decreased in the serum,
hippocampus and prefrontal cortex (PFC) of patients with major depression, which can
be reversed by chronic, but not acute, antidepressant treatments. However, the underlying
mechanisms of how decreased BDNF levels lead to depression and of how increased BDNF
levels provide antidepressant effects remain to be understood. We are trying to address
these underlying mechanisms by focusing on BDNF promoters using promoter specific
mutant mice. Our research goal is to find out how promoter-specific gene regulation
of BDNF is involved in pathogenesis of depression/depression-like behavior and recovery
from mood disorders. We use a multidisciplinary approach from gene to behavior with
genetic, molecular and biochemical, electrophysiological, and behavioral techniques.
While major depression is the leading disease burden in industrialized countries including
the North America, we believe that understanding the underlying mechanisms will advance
the future therapy for depression.
Brendan Tunstall, PhD
Research Interest: The goal of my research is to better understand the neurobiological
mechanisms that drive drug taking and seeking. My current research aims to define
the role of consummatory- and stress-related neuropeptides in alcohol and opioid dependence.
Of particular interest is the neuropeptide oxytocin. I recently found that when oxytocin
was administered by intraperitoneal, intranasal (a technique also applied in humans),
and intracerebroventricular routes, it could block the escalated drinking that develops
in alcohol-dependent rats. It is my hope that with a combination of behavioral, in
vivo neurobiological (e.g., optogenetics and fiber photometer), and microscopy techniques,
that I will be able to elucidate the role of oxytocin and related brain signaling
elements in this phenomenon.
Thirumalini Vaithianathan, PhD
Research Interest: Synapses are communication points of neurons. Synaptic vesicle
fusion is a tightly controlled process governed by many factors and triggered by localized
calcium levels, Sensory synapses face additional challenges besides to the basic requirements,
that is to be able to transmit extremely fast, precise and sustained neurotransmission
that is critical for the perception of complex senses such as vision and hearing.
The main objective of the research in my laboratory is to understand how retinal bipolar
cells, a class of neuron critical to support both fast transient and slow sustained
release are specialized for these tasks. This work study the components involved in
synaptic vesicle trafficking and localized presynaptic calcium signaling in normal
and degenerative disease utilizing state-of-the-art imaging, electrophysiological,
electron microscopy, and pharmacological tools in retinal bipolar neurons from transgenic
zebrafish and mouse models.
Fu-Ming Zhou, PhD
Research Interest: Dr. Zhou currently conducts a multidisciplinary research program
designed to determine the molecular, cellular and neuropharmacological mechanisms
of the brain monoamine systems. Particular attention is being paid to the contributions
of these monoamine systems to neuropsychiatric disorders such as Parkinson’s disease,
depression, schizophrenia, drug abuse, and attention deficit hyperactivity disorder
(ADHD). We use rodents as our experimental animals. Mutant mice are also used.
Several techniques are used in the laboratory:
- Electrophysiology-patch clamp
- Single cell RT-PCR (in combination with patch clamp)
- Electrochemistry (fast cyclic voltammetry at the carbon fiber microelectrode; HPLC)
- Immunohistochemistry
Dr. Zhou's research is funded by R01 grants from the National Institute on Drug Abuse and National Institute of Mental Health and grants from private foundations.
Ioannis Dragatsis, PhD
Research Interest:
Project 1 Title: Analysis of a mouse model for Familial Dysautonomia
Familial Dysautonomia (FD) is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, leading to death before the age of 40. The disease is characterized by progressive degeneration of the sensory and autonomic nervous system. Despite the identification of the gene that causes FD (Ikbkap) and recent medical advances, no cure is available. We have generated a mouse model recapitulating the phenotypic features of the disease and our goal is to elucidate the mechanisms that lead to neuronal degeneration in FD and to test therapeutic strategies.
Project 2 Title: Analysis of the function(s) of huntingtin
Huntington's disease (HD) is an autosomal dominant disorder that affects 1 in 10,000 individuals. HD is characterized by chorea, rigidity and progressive dementia. Symptoms usually begin between the ages of 35 and 50 years, with death typically following 15 to 20 years later. HD is caused by the expansion of an unstable stretch of CAG triplet repeats within the coding region of the HD gene. Moreover the protein encoded by the HD gene, huntingtin, is a novel protein of unknown function.
We are using the mouse as a model organism. Inactivation of the mouse homologue of the HD gene results in embryonic lethality demonstrating that huntingtin is essential for early embryonic development. Conditional inactivation of the gene at later stages results in progressive neurodegeneration in the adult mouse, suggesting that huntingtin is also essential for neuronal survival.
Valerie Vasquez, PhD
Research Interest: Mechanosensitive ion channels translate mechanical stimuli into
an electrochemical signal, which ultimately leads to physiological or perceptual responses.
Some of these responses in humans include touch, pain, proprioception, hearing, and
blood pressure regulation. These channels do not share a common topology and so far
five classes of membrane proteins have been proposed to form mechanosensitive channels
in eukaryotes: the amiloride-sensitive sodium channels (DEG/ENaCs), the transient
receptor potential channels (TRPs), the two-pore domain K+ channels (K2Ps), the Piezo
proteins, and the transmembrane channel-like proteins (TMCs). We are particularly
interested on identifying membrane lipids that regulate channel function in vivo and
the mechanism by which they interact to give rise to mechano-dependent gating.
Our lab aims to understand the functional, structural, and molecular mechanism by which mechanosensitive channels respond to mechanical stimuli and help delineate a general framework for their roles in health and disease. We follow two main avenues: 1) in vitro biochemical and biophysical approaches to study protein-protein and protein-lipid interactions of bona fide mechanosensitive channel complexes, and 2) in vivo approaches to characterize mechanosensitive channels in C. elegans having novel physiological roles.