Heidi Chial, PhD

Professional Titles

• Director of Grant Strategy and Development, University of Colorado Alzheimer's and Cognition Center

Recognitions

• Butler-Williams Scholar, NIH National Institute on Aging (NIA) (2023)
  Selected to participate in this NIA-sponsored program that provides unique opportunities for junior faculty and researchers who are new to the field of aging to gain insight about research on aging from a number of perspectives.

Research Interests

I have extensive experience and a long-standing interest in using cell biological and genetic approaches to uncover mechanistic links between chromosomal aneuploidy and human disease. My studies of aneuploidy began as a graduate student in Dr. Mark Winey’s laboratory at the University of Colorado-Boulder, where I discovered a shared localization of yeast Ndc1p to spindle poles and nuclear pore complexes and I identified NDC1 gene dosage effects — both haploinsufficiency and overexpression — that lead to genetic instability and aneuploidy in yeast. Based on these findings, we hypothesized that the phenotypes associated with altered NDC1 gene dosage and its ability to induce aneuploidy could serve as a model for understanding human diseases associated with genetic instability, including cancer and neurodegenerative disease. In my postdoctoral training, I worked in cancer biology labs at the Mayo Clinic College of Medicine and Wake Forest University School of Medicine, and then pursued additional training in molecular and cellular neuroscience at the Marine Biological Laboratory and at Stanford University School of Medicine. At Stanford University, my research was aimed at understanding the role of a pair of RAB5 effectors — called APPL1 and APPL2 — in neurotrophin- and endosome-mediated signaling pathways in neurodegenerative disease with a special focus on the connections between Alzheimer’s disease and Down syndrome/Trisomy 21. Since joining Dr. Potter’s research group at the University of Colorado Alzheimer's and Cognition Center in 2015, I have been involved in the design, implementation, analysis, and publication of research projects focused on the connections between aneuploidy, Alzheimer’s disease, and other forms of neurodegenerative disease, such as frontotemporal lobar degeneration (FTLD) and Huntington’s disease, links between Alzheimer’s disease and Down syndrome, and developing novel Alzheimer’s disease therapeutics.

Publications

• Caneus J, Granic A, Rademakers R, Dickson DW, Coughlan CM, Chial HJ, Potter H. Mitotic Defects Lead to Neuronal Aneuploidy and Apoptosis in Frontotemporal Lobar Degeneration Caused by MAPT Mutations. Mol Biol Cell. 2017 Dec 27. [Epub ahead of print] PubMed PMID: 29282277
• Hamlett ED, Ledreux A, Potter H, Chial HJ, Patterson D, Espinosa JM, Bettcher BM, Granholm AC. Exosomal biomarkers in Down syndrome and Alzheimer's disease. Free Radic Biol Med. 2018 Jan;114:110-121. PubMed PMID: 28882786
• Chial HJ, Lenart P, Chen YQ. APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy. PLoS One. 2010 Aug 30;5(8):e12471. PubMed PMID: 20814572
• Chial HJ, Wu R, Ustach CV, McPhail LC, Mobley WC, Chen YQ. Membrane targeting by APPL1 and APPL2: dynamic scaffolds that oligomerize and bind phosphoinositides. Traffic. 2008 Feb;9(2):215-29. PubMed PMID: 18034774
• Chial HJ, Stemm-Wolf AJ, McBratney S, Winey M. Yeast Eap1p, an eIF4E-associated protein, has a separate function involving genetic stability. Curr Biol. 2000 Nov 30;10(23):1519-22. PubMed PMID: 11114520
• Chial HJ, Winey M. Mechanisms of genetic instability revealed by analysis of yeast spindle pole body duplication. Biol Cell. 1999 Jul;91(6):439-50. PubMed PMID: 10519004
• Chial HJ, Giddings TH Jr, Siewert EA, Hoyt MA, Winey M. Altered dosage of the Saccharomyces cerevisiae spindle pole body duplication gene, NDC1, leads to aneuploidy and polyploidy. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10200-5. PubMed PMID: 10468586
• Chial HJ, Rout MP, Giddings TH, Winey M. Saccharomyces cerevisiae Ndc1p is a shared component of nuclear pore complexes and spindle pole bodies. J Cell Biol. 1998 Dec 28;143(7):1789-800. PubMed PMID: 9864355
• Chial HJ, Splittgerber AG. A comparison of the binding of Coomassie brilliant blue to proteins at low and neutral pH. Anal Biochem. 1993 Sep;213(2):362-9. PubMed PMID: 7694522
• Chial HJ, Thompson HB, Splittgerber AG. A spectral study of the charge forms of Coomassie blue G. Anal Biochem. 1993 Mar;209(2):258-66. PubMed PMID: 7682385
• Caneus, J., Granic, A., Chial, H.J., and Potter, H. (2017) Using Fluorescence In Situ Hybridization (FISH) Analysis to Measure Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative Diseases. In Genomic Mosaicism in Neurons and Other Cell Types. Eds. Jose M. Frade and Fred H. Gage, Neuromethods, Humana Press, 131: 329-359.
• Huntington Potter, Julbert Caneus, Antoneta Granic, Steven P. Bennett, and Ching-Jung Wang, Heidi J. Chial. “Systemic Cell Cycle Defects in Neurodegenerative Diseases.” Systems Biology of the Cell Cycle: Towards Integration with Cell Physiology. Ed. M. Barberis. New York: Springer (In Press).
• Potter H, Chial HJ, Caneus J, Elos M, Elder N, Borysov S, Granic A. Chromosome Instability and Mosaic Aneuploidy in Neurodegenerative and Neurodevelopmental Disorders. Front Genet. 2019;10:1092. PubMed PMID: 31788001
• Potter H, Chial HJ. Targeting the Interaction Between Apolipoprotein E and Amyloid Precursor Protein: A Novel Alzheimer's Disease Therapy. Biol Psychiatry. 2019 Aug 1;86(3):169-170. PubMed PMID: 31319935
• Potter, H., Woodcock, J.H., Boyd, T.D. Coughlan, C.M., O’Shaughnessy, J.R., Borges, M.T., Thaker, A.A., Raj, B.A., Adamszuk, K., Scott, D., Adame, V., Chial., H.J., Gray, H., Daniels, J., Stocker, M.E., Sillau, S.H. Safety and Efficacy of Sargramostim in the Treatment of Alzheimer’s Disease. Alzheimer’s & Dementia: Translational Research & Clinical Interventions (2021), In Press.
• Coughlan C, Bruce KD, Burgy O, Boyd TD, Michel CR, Garcia-Perez JE, Adame V, Anton P, Bettcher BM, Chial HJ, Königshoff M, Hsieh EWY, Graner M, Potter H. Exosome Isolation by Ultracentrifugation and Precipitation and Techniques for Downstream Analyses. Curr Protoc Cell Biol. 2020 Sep;88(1):e110. PubMed PMID: 32633898
• Ahmed MM, Johnson NR, Boyd TD, Coughlan C, Chial HJ, Potter H. Innate Immune System Activation and Neuroinflammation in Down Syndrome and Neurodegeneration: Therapeutic Targets or Partners?. Front Aging Neurosci. 2021;13:718426. PubMed PMID: 34603007
• Rajic AJ, Pressman PS, Woodcock JH, Chial HJ, Filley CM. Use of coffee grounds to test olfaction for predicting cognitive dysfunction and decline. J Neurol Sci. 2021 Aug 15;427:117516. PubMed PMID: 34111761
• Potter H, Woodcock JH, Boyd TD, Coughlan CM, O'Shaughnessy JR, Borges MT, Thaker AA, Raj BA, Adamszuk K, Scott D, Adame V, Anton P, Chial HJ, Gray H, Daniels J, Stocker ME, Sillau SH. Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease. Alzheimers Dement (N Y). 2021;7(1):e12158. PubMed PMID: 33778150
• Coughlan C, Bruce KD, Burgy O, Boyd TD, Michel CR, Garcia-Perez JE, Adame V, Anton P, Bettcher BM, Chial HJ, Königshoff M, Hsieh EWY, Graner M, Potter H. Exosome Isolation by Ultracentrifugation and Precipitation and Techniques for Downstream Analyses. Curr Protoc Cell Biol. 2020 Sep;88(1):e110. PubMed PMID: 32633898
• Secora C, Vielle A, Wang AC-J, Lenhart P, Salcedo E, Johnson NR, Ahmed MM, Chial HJ, Boyd TD, Potter H, and Vergara MN (2021). Traumatic Brain Injury Exacerbates Alzheimer's Disease Pathology in the Retinas of TgF344-AD Rats. bioRxiv, 2021.2009.2023.461334. doi: https://doi.org/10.1101/2021.09.23.461334.
• Esteban M. Lucero, Ronald K. Freund, Noah R. Johnson, Breanna Dooling, Emily Sullivan, Olga Prikhodko, Md. Mahiuddin Ahmed, Mark L. Dell'Acqua, Heidi J. Chial, Huntington Potter. Kif11 overexpression rescues cognition, long-term potentiation, and spine defects in mouse and cell models of Alzheimer's disease. bioRxiv 2021.09.09.459627; doi: https://doi.org/10.1101/2021.09.09.459627.
• Md. Mahiuddin Ahmed, Athena Ching-Jung Wang, Mihret Elos, Heidi J. Chial, Stefan Sillau, D. Adriana Solano, Christina Coughlan, Leila Aghili, Paige Anton, Neil Markham, Vanesa Adame, Katheleen J. Gardiner, Timothy D. Boyd, Huntington Potter. Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice. bioRxiv 2021.07.04.451073; doi: https://doi.org/10.1101/2021.07.04.451073.
• Noah R. Johnson, Athena C.-J. Wang, Christina Coughlan, Stefan Sillau, Esteban Lucero, Lisa Viltz, Neil Markham, Cody Allen, A. Ranjitha Dhanasekaran, Heidi J. Chial, Huntington Potter. Imipramine and olanzapine block apoE4-catalyzed polymerization of Aß and show evidence of improving Alzheimer’s disease cognition. bioRxiv 2021.03.28.437389; doi: https://doi.org/10.1101/2021.03.28.437389.
• Lucero EM, Freund RK, Smith A, Johnson NR, Dooling B, Sullivan E, Prikhodko O, Ahmed MM, Bennett DA, Hohman TJ, Dell'Acqua ML, Chial HJ, Potter H. Increased KIF11/kinesin-5 expression offsets Alzheimer Aß-mediated toxicity and cognitive dysfunction. iScience. 2022 Nov 18;25(11):105288. PubMed PMID: 36304124
• Pressman PS, Chen KH, Casey J, Sillau S, Chial HJ, Filley CM, Miller BL, Levenson RW. Incongruences Between Facial Expression and Self-Reported Emotional Reactivity in Frontotemporal Dementia and Related Disorders. J Neuropsychiatry Clin Neurosci. 2022 Aug 22;:appineuropsych21070186. [Epub ahead of print] PubMed PMID: 35989572
• Johnson NR, Wang AC, Coughlan C, Sillau S, Lucero E, Viltz L, Markham N, Allen C, Dhanasekaran AR, Chial HJ, Potter H. Imipramine and olanzapine block apoE4-catalyzed polymerization of Aß and show evidence of improving Alzheimer's disease cognition. Alzheimers Res Ther. 2022 Jun 29;14(1):88. PubMed PMID: 35768831
• Ahmed MM, Wang AC, Elos M, Chial HJ, Sillau S, Solano DA, Coughlan C, Aghili L, Anton P, Markham N, Adame V, Gardiner KJ, Boyd TD, Potter H. The innate immune system stimulating cytokine GM-CSF improves learning/memory and interneuron and astrocyte brain pathology in Dp16 Down syndrome mice and improves learning/memory in wild-type mice. Neurobiol Dis. 2022 Jun 15;168:105694. PubMed PMID: 35307513
• Galvin J, Curran E, Arteaga F, Goossens A, Aubuchon-Endsley N, McMurray MA, Moore J, Hansen KC, Chial HJ, Potter H, Brodsky JL, Coughlan CM. Proteasome activity modulates amyloid toxicity. FEMS Yeast Res. 2022 Mar 9;22(1). PubMed PMID: 35150241
• Pressman PS, Chen KH, Casey J, Sillau S, Chial HJ, Filley CM, Miller BL, Levenson RW. Incongruences Between Facial Expression and Self-Reported Emotional Reactivity in Frontotemporal Dementia and Related Disorders. J Neuropsychiatry Clin Neurosci. 2023 Spring;35(2):192-201. PubMed PMID: 35989572
• Ethan James, Anne Vielle, Karen Cusato, Helen Li, Byoungin Lee, Shama Parween, Anna C. Howell, Noah Johnson, Heidi J Chial, Huntington Potter, M Natalia Vergara. Human iPSC-derived retinal organoids develop robust Alzheimer’s disease neuropathology (In Press, Frontiers in Cellular Neuroscience).

Practice Locations

UCHealth Neurosciences Center - Anschutz Medical Campus
1635 Aurora Ct
4th Floor
Aurora, CO 80045
720-848-2080