Cellular and Molecular Pharmacology Discipline

Center for Neurodegenerative Diseases and Therapeutics

Judy Potashkin graduated from Lehigh University in Bethlehem, PA in 1977.  She earned her MS degree in Cell Biology and Biochemistry at Pennsylvania State University in 1979 and went on to earn a PhD in Molecular Biology from Roswell Park Memorial Institute (Buffalo, NY) in 1985.  Following postdoctoral work at the Cold Spring Harbor Laboratory, she joined the faculty of the Chicago Medical School in 1990 in the Cellular & Molecular Pharmacology discipline. Dr. Potashkin is currently a tenured Professor and CMS Director of Faculty Recognition and Development.

Research

The focus of our research is directed at understanding how the disruption of the regulation of RNA metabolism leads to neurodegeneration. Initially, we tested the hypothesis that expression of RNA is dysregulated in whole blood of Parkinson’s disease patients and therefore measuring RNA abundance would be helpful in identifying RNA biomarkers. In our study, we identified RNA biosignatures that are useful for distinguishing Parkinson’s disease patients from healthy controls and progressive supranuclear palsy and multiple system atrophy patients.  We are testing the markers to see if they are useful for identifying individuals “at risk” for Parkinson’s disease and monitoring the progression of the disease.

We are also investigating the dysregulated pathways and molecular networks that are shared between Parkinson’s disease and Alzheimer’s disease and type II diabetes using bioinformatic approaches.  From these studies we have identified additional biomarkers for Parkinson’s disease and dementia.  We expect that these markers may be useful for clinical studies designed to identify nutrients and diets that may be beneficial for patients. In addition, novel therapeutic targets may be identified.

Publications

Santiago J.A., Quinn J.P. and Potashkin J.A. (2022) Physical Activity Rewires the Human Brain against Neurodegeneration. Int J Mol Sci. 23(11):6223. doi: 10.3390/ijms23116223, PMID: 35682902.

Bottero, V., Santiago J.A., Quinn J.P. and Potashkin J.A. (2022) Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons. Frontiers Molecular Neuroscience 15:825031. doi: 10.3389/fnmol.2022.825031. eCollection 2022. PMID: 35370543.

Bottero V., Alrafati, F., Santiago J.A., Potashkin JA. (2021) Transcriptomic and Network Meta-Analysis of Frontotemporal Dementias. Front Mol Neurosci, section Brain Disease Mechanisms. 14:747798; doi: 10.3389/fnmol.2021.747798. eCollection 2021. PMID: 34720873.

Santiago J.A., Quinn J.P. and Potashkin J.A. (2021) Network Analysis Identifies Sex‐Specific Gene Expression Changes in Blood of Amyotrophic Lateral Sclerosis Patients. Int J Mol Sci. 22, 7150.

Bottero, V., Powers, D., Yalamanchi, A., Quinn, J.P. and Potashkin, J.A. (2021) Key Disease Mechanisms Linked to Alzheimer’s Disease in the Entorhinal Cortex. Int J Mol Sci. 22(8) 3915; https://doi.org/10.3390/ijms22083915.

Santiago J.A. and Potashkin J.A. (2021) The impact of disease comorbidities in Alzheimer’s disease. Frontiers Aging Neuroscience, 13:631770. doi: 10.3389/fnagi.2021.631770

Bottero, V. and Potashkin, J.A., (2020) A Comparison of Gene Expression Changes in the Blood of Individuals Consuming Diets Supplemented with Olives, Nuts or Long-Chain Omega-3 Fatty Acids, Nutrients 12, (12): 3765, https://doi.org/10.3390/nu12123765.

Potashkin, J.A., Bottero, V., Santiago, J.A. and Quinn, J.P. (2020) Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene, Int J Mol Sci. 21(11):E3787. doi: 10.3390/ijms21113787.

Santiago J.A., Bottero V. and Potashkin J.A. (2020) Transcriptomic and Network Analysis Identifies Shared and Unique Pathways across Dementia Spectrum Disorders. Int J Mol Sci. 21: 2050.

Potashkin, J.A., Bottero, V., Santiago, J.A. and Quinn, J.P. (2020) Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene. Int J Mol Sci. 21:3787.

Santiago JA, Bottero V, Potashkin JA.  (2019) Transcriptomic and Network Analysis Highlight the Association of Diabetes at Different Stages of Alzheimer’s Disease. Front. Neurosci. 13:1273.

Bottero V, Potashkin JA.  (2019) Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer's Disease Dementia.  Int J Mol Sci. 20:5403.

Potashkin JA, Bottero V, Santiago JA, Quinn JP.  (2019) Computational identification of key genes that may regulate gene expression reprogramming in Alzheimer's patients.  PLoS One. 14:e0222921.

Bottero V, Santiago JA, Potashkin JA. (2018) PTPRC Expression in Blood is Downregulated in Parkinson's and Progressive Supranuclear Palsy Disorders.  J Parkinsons Dis. 8:529-537.

Santiago JA, Bottero V, Potashkin JA. (2018) Evaluation of RNA Blood Biomarkers in the Parkinson's Disease Biomarkers Program.   Front Aging Neurosci. 10:157.

Santiago JA, Bottero V, Potashkin JA. (2017) Biological and Clinical Implications of Comorbidities in Parkinson's Disease.  Front Aging Neurosci. 9:394.

Santiago JA, Potashkin JA. (2017) Evaluation of RNA Blood Biomarkers in Individuals at Risk of Parkinson's Disease. J Parkinsons Dis. 7:653.

Gwinn K, David KK, Swanson-Fischer C, Albin R, Hillaire-Clarke CS, Sieber BA, Lungu C, Bowman FD, Alcalay RN, Babcock D, Dawson TM, Dewey RB Jr, Foroud T, German D, Huang X, Petyuk V, Potashkin JA, Saunders-Pullman R, Sutherland M, Walt DR, West AB, Zhang J, Chen-Plotkin A, Scherzer CR, Vaillancourt DE, Rosenthal LS. (2017) Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program. Biomark Med. 11:451-473.

Santiago JA, Bottero V, Potashkin JA. (2017) Dissecting the Molecular Mechanisms of Neurodegenerative Diseases through Network Biology. Front Aging Neurosci. 9:166

Santiago JA, Potashkin JA. (2017) Blood Transcriptomic Meta-analysis Identifies Dysregulation of Hemoglobin and Iron Metabolism in Parkinson' Disease. Front Aging Neurosci. 9:73.

Santiago JA, Littlefield AM, and Potashkin JA. (2016) Integrative transcriptomic meta-analysis of Parkinson's disease and depression identifies NAMPT as a potential blood biomarker for de novo Parkinson's disease. Sci Rep. 6:34579.

Santiago, J.A., and Potashkin, J.A. (2015) Blood Biomarkers Associated with Cognitive Decline in Early Stage and Drug-Naive Parkinson's Disease Patients. PLoS One. 10:e0142582.

Santiago, J.A, and Potashkin, J.A. (2015) Network-based meta-analysis identifies HNF4A and PTBP1 as longitudinally dynamic biomarkers for Parkinson’s disease, Proc. Natl. Acad. Sci, 112:2257-62.

Santiago, J. A., Bilyk, H. and Potashkin, J.A. (2014) Understanding the Role Diet Plays in Parkinson’s Disease Could Lead to Better Disease Management. Clin Exp Pharmacol, 5: e135.

Santiago, J.A and Potashkin, J.A. (2014) A network approach to clinical intervention in neurodegenerative diseases, Trends in Mol Med, 20:694-703.

Santiago, J.A, Scherzer, C.R. and Potashkin, J.A.  (2014) Network analysis identifies SOD2 mRNA as a potential biomarkers for Parkinson’s Disease” PLoS One, 9:e109042.

Santiago, J.A and Potashkin, J.A. (2014) Current challenges towards the development of a blood test for Parkinson’s disease.  Diagnostics 4:153-164. doi:10.3390/diagnostics4040153. 

Santiago J.A. and Potashkin J.A. (2014) System-based approaches to decode the molecular links in Parkinson's disease and diabetes. Neurobiol Dis. 2014 Apr 6. pii: S0969-9961(14)00080-1. doi: 10.1016/j.nbd.2014.03.019. [Epub ahead of print]

Seidl S.E., Santiago J.A., Bilyk H., and Potashkin J.A. (2014) The emerging role of nutrition in Parkinson's disease. Front Aging Neurosci. 2014 Mar 7;6:36.

Santiago, J.A. and Potashkin, J.A. (2014) A Network Approach to Diagnostic Biomarkers in Progressive Supranuclear Palsy, Movement Disorders, 29:550-5.

Santiago, J.A. and Potashkin, J.A. (2013) Integrative network analysis unveils convergent molecular pathways in Parkinson’s disease and diabetes, PLoS One, 8:e83940.

Santiago, J.A., Scherzer, C. R., Harvard Biomarker Study, and Potashkin, J.A. (2013) Specific splice variants are associated with Parkinson’s disease, Movement Disorders, 28:1724-7.

Santiago J.A. and Potashkin J.A. (2013) Shared dysregulated pathways lead to Parkinson's disease and diabetes. Trends Mol Med. 19:176-86.

Potashkin J.A, Santiago J.A., Ravina B.M., Watts A., and Leontovich A.A. (2013) Biosignatures for Parkinson's disease and atypical parkinsonian disorders patients. PLoS One. 2012;7(8):e43595.

Seidl S.E., and Potashkin J.A. (2011) The promise of neuroprotective agents in Parkinson's disease. Front Neurol. 2:68.

Wentz-Hunter K.K. and Potashkin J.A. (2011) The Role of miRNAs as Key Regulators in the Neoplastic Microenvironment.  Mol Biol Int. 2011:839872.

Potashkin J.A., Blume SR, Runkle NK. (2010) Limitations of animal models of Parkinson's disease. Parkinsons Dis. 2011:658083.

Wu, J.Y. and Potashkin, J.A. (2009) Alternative splicing in the nervous system. Encyclopedia of Neuroscience, (L.R. Squire, Editor). Oxford: Academic Press. 1:245-251.

Zhou L., Qi X., Potashkin J.A., Abdul-Karim F.W. and Gorodeski G.I. (2008) Micro-RNAs miR-186 and miR-150 downregulate expression of the pro-apoptotic purinergic P2X7 receptor by activation of instability sites at the 3'-untranslated region of the gene that decrease steady-state levels of the transcript. J. Biol. Chem. 283:28274-28286.

Meredith, G.E., Totterdell S., Potashkin J.A. and Surmeier D.J. (2008) Modeling PD pathogenesis in mice: advantages of a chronic MPTP protocol. Parkinsonism Relat. Disord. 14 Suppl 2:S112-115.

Potashkin J.A., Kang U.J., Loomis P.A., Jodelka F.M., Ding Y. and Meredith G.E. (2007) MPTP administration in mice changes the ratio of splice isoforms of fosB and rgs9. Brain Res. 1182:1-10.

Marinescu V., Loomis P.A., Ehmann S., Beales M. and Potashkin J.A. (2007) Regulation of retention of FosB intron 4 by PTB. PLoS ONE. 2007 Sep 5;2(9):e828.

Li X., Qi X., Zhou L., Catera D., Rote N.S., Potashkin J., Abdul-Karim F.W. and Gorodeski G.I. (2007) Decreased expression of P2X7 in endometrial epithelial pre-cancerous and cancer cells. Gynecol. Oncol. 106:233-243.

Alibhai I.N., Green T.A., Potashkin J.A. and Nestler E.J. (2007) Regulation of fosB and DeltafosB mRNA expression: in vivo and in vitro studies. Brain Res. 1143:22-33.

Potashkin J.A. and Meredith G.E. (2006) The role of oxidative stress in the dysregulation of gene expression and protein metabolism in neurodegenerative disease. Antioxid. Redox. Signal. 8:144-151.

Wood, V., ... Potashkin, J., ... and Nurse, P. (2002) The genome sequence of Schizosaccharomyces pombe. Nature 21:871-880.

Ochotorena, I.L., Hirata D., Kominami K., Potashkin J., Sahin F., Wentz-Hunter K., Gould K.L., Sato K., Yoshida Y., Vardy L., and Toda T. (2001) Conserved Wat1/Pop3 WD-repeat protein of fission yeast secures genome stability through microtubule integrity and may be involved in mRNA maturation. J. Cell Sci. 114:2911-2920.

Käufer, N.F. and Potashkin, J. (2000) Analysis of the splicing machinery in fission yeast: a comparison with budding yeast and mammals. Nucl. Acids Res. 28:3003-3010.

Mayes, A.E., Potashkin, J. and Beggs, J. (2000) Splicing of pre-mRNA introns. In The Frontiers in Molecular Biology Series: The Yeast Nucleus, Eds. P. Fantes and J. D. Beggs, IRL Press, Oxford.

Beales, M., Flay, N., McKinney, R., Habara, Y., Ohshima, Y. Tani, T., and Potashkin, J. (2000) Mutations in the large subunit of U2AF disrupt pre-mRNA splicing, cell cycle progression and nuclear structure. Yeast 16:1001-10013.

Potashkin, J., Kim, D., Fons, M., Humphrey, T. and Frendewey, D. (1998) Cell division cycle defects associated with fission yeast pre-mRNA splicing mutants. Curr. Genet. 34:153-163.

Gozani, O., Potashkin, J. and Reed, R. (1998) Recruitment of U2 snRNP to the branchpoint sequence via direct interactions with U2AF. Mol. Cell. Biol. 18:4752-4760.

Potashkin J., Wentz-Hunter K. and Callaci, J. (1996) BTF3 is evolutionarily conserved in fission yeast. Biochim. Biophys. Acta. 1308:182-184.

McKinney, R., Wentz-Hunter, K., Schmidt, H., and Potashkin, J. (1997)Molecular characterization of a novel fission yeast gene spUAP2 that interacts with the splicing factor spU2AF59. Curr. Genet. 32:323-330.

Wentz-Hunter, K. and Potashkin, J. (1996) The small subunit of the splicing factor U2AF is conserved in fission yeast. Nucl. Acids Res. 24:1849-1854.

Wentz-Hunter, K. and Potashkin, J. (1995) The evolutionary conservation of the splicing apparatus between fission yeast and man. Nucleic Acids Symposium Series 33:226-228.

Potashkin, J., Naik, K. and Wentz-Hunter, K. (1993) U2AF homolog required for splicing in vivo. Science 262:573-575.

Potashkin, J.A., Derby R.J. and Spector D.L. (1990) Differential distribution of factors involved in pre-mRNA processing in the yeast cell nucleus. Mol. Cell. Biol. 10:3524-3534.

Frendewey D., Barta I., Gillespie M. and Potashkin J. (1990) Schizosaccharomyces U6 genes have a sequence within their introns that matches the B box consensus of tRNA internal promoters. Nucleic Acids Res.18:2025-2032.

Potashkin J. and Frendewey D. (1990)A mutation in a single gene of Schizosaccharomyces pombe affects the expression of several snRNAs and causes defects in RNA processing. EMBO J. 9:525-534.

Potashkin J. and Frendewey D. (1989) Splicing of the U6 RNA precursor is impaired in fission yeast pre-mRNA splicing mutants. Nucleic Acids Res. 17:7821-7831.

Potashkin J., Li R., and Frendewey D. (1989) Pre-mRNA splicing mutants of Schizosaccharomyces pombe. EMBO J. 8:551-559.

Potashkin J.A. and Beach D.H. (1988) Multiple phosphorylated forms of the product of the fission yeast cell division cycle gene cdc2+. Curr. Genet. 14:235-240.

Draetta G., Brizuela L., Potashkin J. and Beach D. (1987) Identification of p34 and p13, human homologs of the cell cycle regulators of fission yeast encoded by cdc2+ and suc1+. Cell. 50:319-325.

Potashkin J.A. and Huberman J.A. (1986) Characterization of DNA sequences associated with residual nuclei of Saccharomyces cerevisiae. Exp. Cell Res. 165:29-40.

Potashkin J.A., Zeigel R.F. and Huberman J.A. (1984) Isolation and initial characterization of residual nuclear structures from yeast. Exp. Cell Res. 153:374-388.

Potashkin J.A. and Schlegel R.A. (1980) A possible mechanism by which SV40 T-antigen stimulates rRNA synthesis. Cell Biol. Int. Rep. 4:399-406.

Editorials

Santiago, J. A., Bilyk, H. and Potashkin, J.A. Understanding the Role Diet Plays in Parkinson’s Disease Could Lead to Better Disease Management. Clin Exp Pharmacol, in press.

Santiago, J.A and Potashkin, J.A. (2013) Network Analysis Accelerates Understanding of Disease Mechanisms. Clin Exp Pharmacol 3: e123.

Potashkin, J.A., (2010) Biomarkers Of Neurodegeneration That Would Please A Vampire. Frontiers in Neuroscience. 4:134-135. NIHMSID # 309729

Potashkin, J.A., MiRNAs, (2010) Cause or Cure Frontiers in Neuroscience. Research Highlights 4:140.