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Salvatore Mancarella, PhD

Associate Professor

smancare@uthsc.edu
Phone: 901.448.7348

Mancarella Lab Website

Research Topic

We investigate cellular signals that regulate the functions of the heart and vessels. In particular, our research focuses on the study of calcium microdomains and how their perturbation in cardiac muscle and smooth muscle often results in cardiac and vascular wall diseases, leading cause of death in the modern world. Currently, we are studying the newly discovered intracellular calcium sensors, Stromal Interaction Proteins (STIM1 and STIM2) which are crucial components of these cellular microdomains. We employ high definition confocal microscopy, electrophysiology, and isolated heart technique to characterize the calcium signaling generated in the microdomains and how this travel into the nucleus to start a pathological gene transcription program. We also use animal models of cardiovascular diseases to mimic the human disease process and the calcium signal disarray that undermine such disease in order to explore new therapeutic strategies against cardiovascular disorders.

Honors and Awards

  • 2000 Telethon Research Fellowship
  • 2009 Post Doctoral Fellowship Award American Heart Association
  • 2009 Post Doctoral Fellowship Award National Institutes of Health (F32, NIH/NHLBI)
  • 2013 Scientist Development Award (SDG) American Heart Association
  • 2013 K99/R00 Pathway to Independence Award, National Institutes of Health

Postdoc Opportunities

We are always seeking enthusiastic, self-motivated candidates who are excited to tackle a biologically-intriguing and medically-important disease and be a collaborative member of our laboratory. Ideal candidates will have a MD and/or PhD in biology, biochemistry, chemistry, or related fields. Experience in molecular biology, live cell imaging, and/or animals surgery desired. Excellent English written and spoken skills are necessary.

Graduate Students Opportunities

We are keen to hear from talented students wishing to pursue graduate studies in my lab. Future PhD projects involve researching molecular basis of cardiac diseases and hypertension. Interested individuals should email Prof. Mancarella outlining any research experience and details of classes taken during their undergraduate degree. Potential graduate students can apply through the UTHSC PhD program. Students enrolled in the UTHSC PhD program should also contact Prof Mancarella if they wish to undertake a lab rotation.

Publications

  1. Wang X., Wang Y., Zhou Y., Eunan H., Mancarella S., Andrake M., Rothberg B., Soboloff J., Gill D. L. (2014) Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site. Nature Communiction. PMID 24625331.
  2. Kumar G.R., Meng S., Chandramoorthy H.C., Mallilankaraman K, Mancarella S., Guo H., Razmpour H., Houser S.R., Chen J., Wang H., Soboloff J., Gill D.L., Madesh M. (2013) Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J Clin Invest.  PMID: 23348743
  3. Mancarella S., Potireddy S., Wang Y., Gao H., Gandhirajan R., Autieri M., Scalia R., Cheng Z., Wang H., Madesh M., Houser R. S., Gill D.L. (2013) Targeted STIM Deletion Impairs Calcium Homeostasis, NFAT Activation, and Growth of Smooth Muscle. FASEB J. PMID: 23159931
  4. Mancarella S.*, Robinson L.*, Songsawad D., Tourkova I., Barnett J.J., Gill D.L,, Soboloff J., Blair H. (2012).Gene Disruption of the Calcium Channel Orai1 Results in Inhibition of Osteoclast and Osteoblast Differentiation and Impairs Skeletal Development. Lab. Invest, journal cover. PMID: 22546867.
  5. Mancarella S., Wang Y., Deng X., Landesberg G., Scalia R., Panettieri R.A., Mallilankaraman K., Tang X.D., Madesh M., Gill D.L. (2011).Hypoxia-induced Acidosis Uncouples the STIM-Orai Calcium Signaling Complex. J. Biol. Chem. PMID: 22084246
  6. Mancarella S., Wang Y., Gill D.L. (2011). Signal transduction: STIM1 senses both Ca2+ and heat. Nat. Chem. Biol. PMID 21587254.
  7. Karnabi E., Qu Y., Mancarella S., Boutjdir M. (2011). Rescue and Worsening of Congenital Heart Block-Associated Electrocardiographic Abnormalities in Two Transgenic Mice. J. Cardiovasc. Electrophysiol.  PMID: 21352396.
  8. Wang Y., Deng X.*, Mancarella S.*, Hendron E.*, Eguchi S., Soboloff J., Tang X.D., Gill D.L. (2010). The Calcium Store Sensor STIM1 Reciprocally Controls Orai and CaV1.2 Channels. Science.  PMID: 20929813.
  9. Mancarella S., Wang Y., Gill D.L. (2009) Calcium signals: STIM dynamics mediate spatially unique oscillations. Curr Biol. PMID: 19889372.
  10. Karnabi E., Qu Y., Wadgaonkar R., Mancarella S., Yue Y., Chahine M., Clancy R.M., Buyon J.P., Boutjdir M. (2010). Congenital Heart Block: Identification of Autoantibody Binding Site on the Extracellular Loop (Domain I, S5-S6) of α1D L-type Ca2+ Channel. J. Autoimmun. PMID: 19640679.
  11. Mancarella S.,* Zhou Y.*, Wang Y., Yue C., Ritchie M., Gill D.L. and Soboloff J. (2009). Short N-terminal Domains of STIM1 and STIM2 Control the Activation Kinetics of Orai1 Channels. J. Biol. Chem.  PMID: 19487696.
  12. Karnabi E., Qu Y., Mancarella S., Yue Y., Wadgaonkar R., Boutjdir M. (2009).Silencing of Cav1.2 Gene in Neonatal Cardiomyocytes by Lentiviral Delivered shRNA. Biochem. Biophys. Res. Commun.  PMID: 19422800.
  13. Wang Y., Deng X., Zhou Y., Hendron E., Mancarella S., Ritchie MF., Tang X.D., Kurosaki T., Mori Y., Soboloff J., and Gill D.L. (2009). STIM Protein Coupling in the Activation of Orai Channels. Proc. Natl. Acad. Sci.  PMID: 19376967.
  14. Mancarella S., Yue Y., Qu Y., Karnaby E., El-Sherif N., Boutjdir M. (2008). Impaired Calcium Homeostasis is Associated with Atrial Fibrillation in the α1D L-Type Ca2+ Channel Knockout Mice. Am. J. Physiol. Heart. Circ. Physiol. PMID: 18790836.
  15. Chahine M., Qu Y., Mancarella S., Boutjdir M. (2008). Protein Kinase C Activation Inhibits α1D L-type Ca2+ Channel: a Single-Channel Analysis. Pflugers. Arch. PMID: 17909852
  16. Lehnart S.E., Terrenoire C., Reiken S., Wehrens X.H., Song LS., Tillman E.J., Mancarella S., Coromilas J., Lederer W.J., Kass R.S., Marks A.R. (2006). Stabilization of Cardiac Ryanodine Receptor Prevents Intracellular Calcium Leak and Arrhythmias. Proc. Natl. Acad. Sci.  PMID: 16672364
  17. Srivastava S., Collis L., Go A., Mancarella S., Artman M. (2005).Paradoxal Effect of Dofetilite on Action Potential Duration and Calcium Transient Amplitude in Newborn Rabbit Ventricular Myocytes. J. Cardiovasc. Pharmacol.  PMID: 15654266.
  18. Facchiano F., Fernandez E., Mancarella S., Maira G., Miscusi M., D'Arcangelo D., Cimino-Reale G., Falchetti M.L., Capogrossi M.C., Pallini R. (2002). Promotion of Regeneration of Corticospinal Tract Axons in Rats with Recombinant Vascular Endothelial Growth Factor Alone and Combined with Adenovirus Coding for this Factor. J. Neurosurg.  PMID: 12134907.
  19. Facchiano F., Lentini A., Fogliano V., Mancarella S., Rossi C., Facchiano A., Capogrossi M.C. (2002). Sugar-Induced Modification of Fibroblast Growth Factor 2 Reduces its Angiogenic Activity in-vivo. Am. J. Pathol.  PMID: 12163378.
  20. Gaetano C., Catalano A., Illi B., Felici A., Minucci S., Palumbo R., Facchiano F., Mangoni A., Mancarella S., Muhlhauser J., Capogrossi M.C. (2001). Retinoids Induce Fibroblast Growth Factor-2 Production in Endothelial Cells via Retinoic acid Receptor Alpha Activation and Stimulate Angiogenesis in-vitro and in-vivo. Circ. Res. PMID: 11230116.

Book Chapters

  1. Mancarella S., Srivastava S., Go A., Zhou Y.Y., Coetzee W.A., Artman M. Cardiovascular Development and Congenital Malformation Molecular and Genetic Mechanisms. Chapter 47: Changes in cardiac excitation-contraction coupling during mammalian development: Implications for regulation of contractile fun
May 26, 2022