Bezprozvanny Lab

Research Projects

1. Neuronal calcium signaling as therapeutic target for Alzheimer’s disease. 

Dysregulation of neuronal calcium signaling is one of the key features and likely driver of pathology in Alzheimer’s disease (AD).  Our laboratory discovered the essential role of presenilins in neuronal calcium homeostasis.  We continue to explore a variety of calcium channels, transporters and calcium signaling molecules as potential therapeutic targets for AD treatment.  We reason that this approach may lead to the development of novel disease-modifying agents for AD that can be used as monotherapy or in combination with anti-amyloid treatments. 

2. Sigma 1 receptor – biological function and importance for neurodegeneration.

Normal biological function of Sigma 1 receptors (S1R) is not known. Our laboratory discovered that S1R directly binds to cholesterol and forms cholesterol-enriched microdomains in the endoplasmic reticulum membrane.   We continue to develop this idea and explore its importance for neuroprotective effects of S1R agonists in neurodegenerative disease models and clinical trials.

3. Functional approach to developing therapeutic agents for ataxia.

Dysfunction of cerebellar Purkinje cells plays a key role at early stages of spinocerebellar ataxias (SCA).    Our laboratory demonstrated that positive allosteric modulators of calcium-activated potassium channels normalize function of Purkinje cells in mouse model of SCA2.  Based on these results, we continue to develop and test novel positive allosteric modulators of calcium-activated potassium channels as potential treatment for SCAs. 
 

Meet the PI & Lab Members

Ilya Bezprozvanny, Ph.D., D.Sci

Ilya Bezprozvanny, Ph.D., D.Sci

Professor, Thomsen Chair in Alzheimer’s Disease Research

Ilya Bezprozvanny received M.Sci in Physics (1989, with honors) from the Peter the Great St Petersburg Polytechnical University, St Petersburg, Russia and a Ph.D. in Cell Biology (1992) from the Institute of Cytology Russian Academy of Sciences in St Petersburg, Russia (scientific advisors - Alex P. Naumov and Galina N. Mozhayeva). Ilya performed his postdoctoral training with Barbara E. Ehrlich (1990-1994) at the University of Connecticut Health Center at Farmington, Connecticut and then with Richard W. Tsien (1994-1996) at Stanford University Medical Center, Stanford, California. In 1996, Ilya joined the faculty of UT Southwestern Medical Center at Dallas as an Assistant Professor in the department of Physiology. He was promoted to an Associate Professor (2002) and to a Professor (2007) in the same department. Since 2011 Ilya also holds Carl J. and Hortense M. Thomsen Chair in Alzheimer’s Disease Research. View profile

Caitlynn Knight, B.Sci.

Research Technician
Email

Caitlynn Knight, B.Sci.
See our alumni

Publications

A complete list of published works (129 original papers and 63 invited reviews) is on Research Gate or Google Scholar

Recent and High Impact Publications

  1. T.-S. Tang, H. Tu, E.Y.W. Chan, A. Maximov, Z. Wang, C.L. Wellington, M.R. Hayden, and I. Bezprozvanny. (2003) Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron, v 39, pp 227-239. Pubmed - 12873381
  2. Tu, O. Nelson, A. Bezprozvanny, Z. Wang, S.-F. Lee, Y.-H. Hao, L. Serneels, B.D. Strooper, G. Yu, and I. Bezprozvanny. (2006). Presenilins form ER calcium leak channels, a function disrupted by familial Alzheimer’s disease-linked mutations. Cell, v 126, pp 981-993. Pubmed - 16959576  
  3. W. Kim, Y. Chelliah, S.W. Kim, Z. Otwinowski, and I. Bezprozvanny. (2009) Secondary structure of Huntingtin amino-terminal region. Structure, v 17, pp 1205-1212. Pubmed - 19748341  
  4. Suya Sun, Hua Zhang, Jie Liu,  Elena Popugaeva, Nan-Jie Xu, Stefan Feske,  Charles L. White, III,  and Ilya Bezprozvanny (2014) Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice.  Neuron,  vol 82, pp 79-93. Pubmed - 24698269  
  5. Jun Wu, Hsin-Pei Shih, Vladimir Vigont, Lori Hrdlicka, Len Diggins, Carol Singh, Matt Mahoney, Richard Chesworth, Gideon Shapiro, Olga Zimina, Xuesong Chen, Qingqing Wu, Lyubov Glushankova, Michael Ahlijanian, Gerhard Koenig, Galina N. Mozhayeva, Elena Kaznacheyeva, Ilya Bezprozvanny. (2011)  Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington’s disease treatment.  Chemistry and Biology, v 18, pp 777-793. Pubmed - 21700213  
  6. Adebimpe W. Kasumu, Charlotte Hougaard, Frederik Rode, Thomas A. Jacobsen, Jean Marc Sabatier, Birgitte L. Eriksen, Dorte Strøbæk, Xia Liang, Polina Egorova, Dasha Vorontsova, Palle Christophersen, Lars Christian B. Rønn, and Ilya Bezprozvanny (2012) Selective positive modulator of calcium-activated potassium channels exerts beneficial effects in a mouse model of spinocerebellar ataxia type 2. Chemistry and Biology, vol 19, pp 1340–1353. Pubmed - 23102227  
  7. Suya Sun, Hua Zhang, Jie Liu,  Elena Popugaeva, Nan-Jie Xu, Stefan Feske,  Charles L. White, III,  and Ilya Bezprozvanny (2014) Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice.  Neuron,  vol 82, pp 79-93. Pubmed - 24698269  
  8. Meewhi Kim and Ilya Bezprozvanny (2021). Association with proteasome determines pathogenic threshold of polyglutamine expansion diseases.  Biochemical and Biophysical Research Communications vol 536, pp 95- 99. Pubmed - 33370719  
  9. Vladimir Zhemkov, Jonathon Ditlev, Wan-Ru Lee, Mikaela Wilson, Jen Liou, Michael K. Rosen and Ilya Bezprozvanny.  (2021) The role of sigma-1 receptor in organization of endoplasmic reticulum signaling microdomains.  Elife, vol 10, e65192. Pubmed - 33973848  
  10. Meewhi Kim and Ilya Bezprozvanny (2023). Analysis of non-amyloidogenic mutations in APP supports loss of function hypothesis of Alzheimer’s disease.  J.  Mol. Sci, vol 24, 2092. Pubmed - 36768421  
  11. Zhang H, Knight C, Chen SRW, Bezprozvanny I. (2023) A gating mutation in ryanodine receptor type 2 rescues phenotypes of Alzheimer’s disease mouse models by upregulating neuronal autophagy. The Journal of Neuroscience. vol 43, pp 1441–1454. Pubmed - 36627208  
  12. Pchitskaya Ekaterina, Vasiliev Peter, Daria Smirnova, Chukanov Vyacheslav, and Bezprozvanny Ilya (2023)  SpineTool is an open-source software for analysis of morphology of dendritic spines. Scientific Reports, vol 13. p. 10561. Pubmed - 37386071
  13. Kim M, Bezprozvanny I. Structure-Based Modeling of Sigma 1 Receptor Interactions with Ligands and Cholesterol and Implications for Its Biological Function. International Journal of Molecular Sciences. 2023; 24(16):12980. https://doi.org/10.3390/ijms241612980

Recent Review Articles

  1. Bezprozvanny and M.P. Mattson. (2008) Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease.   Trends in Neuroscience, v. 31, pp 454-463. Pubmed - 18675468  
  2. Bezprozvanny. (2009) Calcium signaling and neurodegeneration.  Trends in Molecular Medicine, v 15, pp 89-100. Pubmed - 19230774  
  3. Polina A. Egorova and Ilya B. Bezprozvanny (2019) Molecular mechanism and therapeutics for spinocerebellar ataxia type 2.   Neurotherapeutics, vol 16, pp. 1050-1073. Pubmed - 31435879  
  4. Daniel A. Ryskamp, Svetlana Korban, Vladimir Zhemkov, Nina Kraskovskaya, and Ilya Bezprozvanny. (2019)   Neuronal Sigma-1 receptors: signaling functions and protective roles in neurodegenerative diseases.    Front Neurosci,  13:862, Pubmed - 31551669  
  5. Ekaterina Pchitskaya and Ilya Bezprozvanny (2020) Dendritic spines shape analysis -classification or clusterization? Synaptic Neurosci. 12:31. Pubmed - 33117142  
  6. Vladimir Zhemkov, Michal Geva, Michael Hayden  and Ilya Bezprozvanny (2021).  Sigma-1 receptor (S1R) interaction with cholesterol: mechanisms of S1R activation and its role in neurodegenerative diseases.  Int. J.  Mol. Sci. vol 22, 4082. Pubmed - 33920913  
  7. Polina Egorova and Ilya Bezprozvanny (2022) Electrophysiological studies support utility of positive modulators of SK channels for treatment of spinocerebellar ataxia type 2.  The Cerebellum, doi:10.1007/s12311-021-01349-1. Pubmed - 34978024  
  8. Ilya Bezprozvanny (2022) Alzheimer’s disease – where do we go from here? Biochemical and Biophysical Research Communications, v 633, pp 72-76. Pubmed - 36344168  
  9. Hua Zhang and Ilya Bezprozvanny (2023). “Dirty Dancing” of Calcium and Autophagy in Alzheimer’s Disease. Life,  vol 13, 1187. Pubmed - 37240832  

Lab News

August 1, 2023

We received R01 R01AG071310

We received R01 R01AG071310 “Calcium dysregulation and vulnerability of entorhinal cortex neurons in Alzheimer's disease” for the period 08/01/23 – 04/30/2028 (MPI together with Dr James Malter).

Contact Us

Email address: Email

Alternative e-mail: Email

Phone Number: (214) 645-6017

Address

Ilya Bezprozvanny, Ph.D. 
Department of Physiology
University of Texas Southwestern Medical Center at Dallas 
6001 Forest Park Rd, ND12.200 
Dallas, Texas 75390-9040
USA

Join Us

Please Email to explain why you are interested in our lab and attach your CV.

Lab Fun

lab lunch

Lab lunch on August 2, 2023

lab lunch

Lab Alumni

  • Vitaly Lupu (1996 – 1999) Neurosurgeon, private practice
  • Elena Kaznacheeva (1996 – 1998) – Lab Head, Institute of Cytology, RAS, St Petersburg
  • Anton Maximov (1997 – 2002) – Associate Professor, Scripps Research Institute, San Diego
  • Elena Nosyreva (1999 – 2002) – Senior Research Scientist, Neuroscience, UTSW
  • Tie-Shan Tang (2000 – 2008) – Lab Head, Institute of Zoology, CAS, Beijing
  • Huiping Tu (2000 – 2007) – group leader, United States Pharmacopeia
  • Sonal Patel (2002 – 2003) – Staff Scientist, UCLA
  • Xi Chen (2004 – 2010) - industry
  • Xuesong Chen (2004 – 2011) - industry
  • Omar Nelson (2005 – 2010) - Assistant Professor, University of Chicago
  • Jun Wu (2006 – 2018) – Senior Research Scientist, Pediatrics, UTSW
  • Jing Liu (2006 – 2009) - Research Scientist, Biochemistry, UTSW
  • Suya Sun (2008 – 2013) – Professor, Shanghai Jiao Tong University of Medicine, Shanghai
  • Adebimpe Kasumu (2009 – 2012) – Neurologist, Northeast Georgia Medical Center Braselton
  • Benjamin Miller (2009 – 2011) - Assistant Professor, Texas Wesleyan University
  • Charlene Supnet (2010 – 2012) - Associate Professor, Neurology, Wash Univ in St. Louis
  • Vladimir Zhemkov (2013 – 2021) – postdoctoral researcher, Cedars-Sinai Medical Center, LA
  • Daniel A. Ryskamp (2014 - 2017) - postdoctoral researcher, Stanford University