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Vytautas Verselis, Ph.D.

Vytautas Verselis, Ph.D.

Professor Emeritus, Dominick P. Purpura Department of Neuroscience

Area of Research: Sensorineural syndromic deafness; biophysical characterization of mutant connexin channels; mouse models with altered Cx hemichannel function; development of pharmacological agents for treatment; mathematical modeling of Cx channels in the nervous system.

Contact Information

718.430.3680vytas.verselis@einsteinmed.edu

Albert Einstein College of Medicine
Rose F. Kennedy Center
1410 Pelham Parkway South, Room 710
Bronx, NY 10461

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Professional Interests

SENSORINEURAL DEAFNESS AND CONNEXIN CHANNEL DYSFUNCTION

Permanent childhood deafness occurs with an incidence of ~1.5 cases per 1000 live births. Approximately 30% of deaf children have cognitive impairment due to the loss of functional interactions among the sensory systems. Although there are a number of genes associated with inherited deafness, mutation of the GJB2 gene encoding the Cx26 gap junction (GJ) protein is the most common. In addition to cognitive impairment and slowed development, there is growing evidence that some Cx26 mutations are linked to developmental cerebellar anomalies. Our studies are currently focusing on a subset of GJB2 mutations that lead to syndromic forms of deafness in which sensorineural hearing loss is accompanied by severe, inflammatory skin disorders, such as keratitis-ichthyosis-deafness (KID) syndrome. Some KID syndrome mutations result in fatality due to uncontrollable sepsis. The underlying basis of KID syndrome and other forms of syndromic deafness appears to be aberrantly behaving hemichannels, a relatively new mechanism identified among Cx-related disorders. Cx hemichannels do not participate in the formation of intercellular GJ channels, but rather remain undocked and function as large, ion channels in the plasma membrane. Mutant hemichannels have been described to behave in a "leaky" manner leading to compromised cell function and cell death. We use a combination of molecular, biophysical and imaging approaches to investigate the mechanisms by which Cx hemichannels are dysfunctional. Planned mouse models will examine contributions of hemichannels in native tissue and provide avenues for treatment. Using explants of the organ of Corti we are examining how Cx channels, both WT and mutant, affect Ca²⁺ dynamics in the cochlea in early postnatal development, which is linked to maturation of hair cells, the principal sensory cells in the cochlea. In addition, we have initiated mathematical modeling of Cx channel gating to better understanding the behavior of Cxs in the cochlea, as well as in neural circuits, in general, where they serve to modulate excitability and coordinate electrical activity.

Selected Publications

Kraujalis T, Gudaitis L, Kraujaliene L, Palacios-Prado N and Verselis VK (2022). The amino terminal domain and modulation of connexin36 gap junction channels by intracellular magnesium ions. Front Physiol 13:839223. PMCID:PMC7642245

Snipas M, Kraujalis T, Maciunas K, Kraujaliene L, Gudaitis L and Verselis VK (2020). Four-state model for simlulating kinetic and steady-state voltage-dependent gating of gap junctions. Biophys J 119(8):1640-1655. PMCID:PMC7642245

Verselis VK (2019). Connexin hemichannels and cochlear function. Neurosci Lett 695:40-45. PMCID:PMC5851822

Srinivas M, Verselis VK and White TW (2018). Human diseases associted with connexin mutations. Biochim Biophys Acta 1860:182-201. PMCID: PMC5659969

Sanchez HA, Slavi N, Srinivas M and Verselis VK (2016). Syndroimic deafness mutations ast Asn 14 differentially alter the open stability of Cx26 hemichannels. J Gen Physiol 148:25-42. PMCID: PMC4924935

Sanchez HA and Verselis VK (2014). Aberrant Cx26 hemichannels and keratitis-ichthyosis-deafness syndrome: Insights into syndromic hearing loss. Front Cell Neurosci 8: Article 354. PMCID: PMC4209889

Sanchez HA, Bienkowski R, Slavi N, Srinivas M and Verselis VK (2014). Altered inhibition of Cx26 hemichannels by pH and Zn²⁺ in the A40V mutation associated with keratitis-ichthyosis-deafness syndrome. J Biol Chem, 289:21519-32. PMCID: PMC4118113

Sanchez HA, Villone K, Srinivas M and Verselis VK (2103). The D50N mutation and syndromic deafness: Altered Cx26 hemichannel properties caused by effects on the pore and intersubunit interactions. J Gen Physiol, 142:3-22. PMCID: PMC3691445

Verselis, VK and Srinivas, M (2013). Connexin channel modulators and their mechanisms of action. Neuropharm, 75:517-24. PMCID: PMC3775990

Sanchez HA, Mese G, Srinivas M, White TW and Verselis VK. (2010). Differentialy altered Ca²⁺ regulation and Ca²⁺ permeability in Cx26 hemichannels formed by the A40V and G45E mutations that cause keratitis-ichthyosis-deafness syndrome. J Gen Physiol, 136:47-62 PMCID: PMC2894548

Verselis VK and Srinivas M (2008). Extracelular divalent cations selectively modulate loop gating, one of two intrinsic forms of voltage dependent gating in connexin hemichannels. J Gen Phys 132:315-27. PMCID: PMC2518728

Chuang CF, VanHoven MK, Fetter RD, Verselis VK and Bargmann, CI. (2007). An innexin-dependent cell network establishes stochastic left-right neuronal asymmetry in C. elegans. Cell 129: 787-99. PMID: 17512411

Srinivas M, Calderon D. P., Kronengold J and Verselis VK (2006). Regulation of connexin hemichannels by monovalent cations. J Gen Phys 127:67-75. PMCID: PMC2151478

Kronengold J, Trexler EB, Bukauskas FF, Bargiello TA and Verselis VK (2003). Single-channel SCAM identifies pore-lining residues in the first extracellular loop and first transmembrane domains of Cx46 hemichannels. J Gen Physiol, 122:389-405. PMCID: PMC2233777

Bukauskas FF, Jordan K, Bukauskiene A, Bennett MVL, Lampe PD, Laird DW and Verselis VK (2000). Clustering of connexin 43-enhanced green fluorescent protein gap junction channels and functional coupling in living cells. Proc Nat Acad Sci (USA), 97:2556-2561. PMCID: PMC15967

Trexler EB, Bennett MVL, Bargiello TA andVerselis VK (1996). Voltage gating and permeation in a gap junction hemichannel. Proc Nat Acad Sci (USA) 93:5836-5841. PMCID: PMC39148

Verselis VK, Ginter CS and Bargiello TA (1994). Opposite voltage gating polarities of two closely related connexins. Nature 368:348-351. PMID: 8127371