Tim D Ahfeldt, PhD
- ASSISTANT PROFESSOR | Neuroscience
- ASSISTANT PROFESSOR | Neurology
Dr. Tim Ahfeldt is an Assistant Professor for Neuroscience. His laboratory carries out translational research using isogenic human pluripotent stem cell models of Parkinson’s Disease (PD) to investigate pathological mechanisms of PD mutations in differentiated midbrain dopaminergic neurons.
Star Family Prize for Excellence in Advising
Derek Bok Award for Distinct Teaching
Aging, Alzheimer's Disease, Developmental Biology, Genetics, Genetics of Movement disorders, Human Genetics and Genetic Disorders, Lysosomes/endosome, Mitochondria, Neuroscience, Parkinson's Disease, Proteomics
We have developed isogenic hPSCs models of complex polygenic diseases, focusing on Parkinson’s disease (PD). Neurodegenerative diseases including PD show a complicated interplay between environment, risk genes specific cell type vulnerability. hPSC isogenic models allow study of disease genes while controlling for genetic background and cell type. Using CRISPR gene editing techniques, we have introduced fluorescent reporters that allow tracking and purification of different neuronal populations. Further we have generated isogenic lines harboring PD causative or associated mutations. We differentiate hPSCs into specific neuronal populations using 3D-spin culture approaches. For example, PD is characterized by the selective vulnerability of nigral midbrain dopaminergic neurons (DANs). Analysis of our PD model through molecular and functional characterization, phenotyping, transcriptomic and proteomic approaches has enabled us to identify novel disease pathways. Our goal is to gain better mechanistic understanding of PD disease pathology to inform new disease modifying therapeutic approaches.
Madison JM, Zhou F, Nigam A, Hussain A, Barker DD, Nehme R, van der Ven K, Hsu J, Wolf P, Fleishman M, O'Dushlaine C, Rose S, Chambert K, Lau FH, Ahfeldt T, Rueckert EH, Sheridan SD, Fass DM, Nemesh J, Mullen TE, Daheron L, McCarroll S, Sklar P, Perlis RH, Haggarty SJ. Characterization of bipolar disorder patient-specific induced pluripotent stem cells from a family reveals neurodevelopmental and mRNA expression abnormalities. Molecular psychiatry 2015 Jun; 20(6).
Lau FH, Deo RC, Mowrer G, Caplin J, Ahfeldt T, Kaplan A, Ptaszek L, Walker JD, Rosengard BR, Cowan CA. Pattern specification and immune response transcriptional signatures of pericardial and subcutaneous adipose tissue. PloS one 2011; 6(10).
Mou H, Zhao R, Sherwood R, Ahfeldt T, Lapey A, Wain J, Sicilian L, Izvolsky K, Musunuru K, Cowan C, Rajagopal J. Generation of multipotent lung and airway progenitors from mouse ESCs and patient-specific cystic fibrosis iPSCs. Cell stem cell 2012 Apr; 10(4).
Ahfeldt T, Schinzel RT, Lee YK, Hendrickson D, Kaplan A, Lum DH, Camahort R, Xia F, Shay J, Rhee EP, Clish CB, Deo RC, Shen T, Lau FH, Cowley A, Mowrer G, Al-Siddiqi H, Nahrendorf M, Musunuru K, Gerszten RE, Rinn JL, Cowan CA. Programming human pluripotent stem cells into white and brown adipocytes. Nature cell biology 2012 Jan; 14(2).
Schinzel RT, Ahfeldt T, Lau FH, Lee YK, Cowley A, Shen T, Peters D, Lum DH, Cowan CA. Efficient culturing and genetic manipulation of human pluripotent stem cells. PloS one 2011; 6(12).
Ding Q, Lee YK, Schaefer EA, Peters DT, Veres A, Kim K, Kuperwasser N, Motola DL, Meissner TB, Hendriks WT, Trevisan M, Gupta RM, Moisan A, Banks E, Friesen M, Schinzel RT, Xia F, Tang A, Xia Y, Figueroa E, Wann A, Ahfeldt T, Daheron L, Zhang F, Rubin LL, Peng LF, Chung RT, Musunuru K, Cowan CA. A TALEN genome-editing system for generating human stem cell-based disease models. Cell stem cell 2013 Feb; 12(2).
Warren L, Manos PD, Ahfeldt T, Loh YH, Li H, Lau F, Ebina W, Mandal PK, Smith ZD, Meissner A, Daley GQ, Brack AS, Collins JJ, Cowan C, Schlaeger TM, Rossi DJ. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell stem cell 2010 Nov; 7(5).
Musunuru K, Strong A, Frank-Kamenetsky M, Lee NE, Ahfeldt T, Sachs KV, Li X, Li H, Kuperwasser N, Ruda VM, Pirruccello JP, Muchmore B, Prokunina-Olsson L, Hall JL, Schadt EE, Morales CR, Lund-Katz S, Phillips MC, Wong J, Cantley W, Racie T, Ejebe KG, Orho-Melander M, Melander O, Koteliansky V, Fitzgerald K, Krauss RM, Cowan CA, Kathiresan S, Rader DJ. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 2010 Aug; 466(7307).
Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nature genetics 2009 Sep; 41(9).
Lau F, Ahfeldt T, Osafune K, Akustsu H, Cowan CA. Induced pluripotent stem (iPS) cells: an up-to-the-minute review. F1000 biology reports 2009 Nov; 1.
Maherali N, Ahfeldt T, Rigamonti A, Utikal J, Cowan C, Hochedlinger K. A high-efficiency system for the generation and study of human induced pluripotent stem cells. Cell stem cell 2008 Sep; 3(3).
Park IH, Arora N, Huo H, Maherali N, Ahfeldt T, Shimamura A, Lensch MW, Cowan C, Hochedlinger K, Daley GQ. Disease-specific induced pluripotent stem cells. Cell 2008 Sep; 134(5).
Ahfeldt T, Litterman NK, Rubin LL. Studying human disease using human neurons. Brain research 2017 Feb; 1656.