Alessandra Chesi, PhD

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Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
Department of Pathology and Laboratory Medicine
University of Pennsylvania Perelman School of Medicine
Room 605A, Stellar Chance Laboratories
422 Curie Blvd.
Philadelphia, PA 19104
Education:
M.Sc. (Physics)
University of Pisa, Italy, 2002.
PhD (Structural and Functional Genomics)
International School for Advanced Studies (SISSA/ISAS), Trieste, Italy, 2007.
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Description of Research Expertise

Research Interests:
Our lab's goal is to translate genetics findings from GWAS and sequencing studies of human neurodegenerative disorders into molecular mechanisms of disease, with the aim of identifying actionable target genes.

Keywords:
neurogenetics, bioinformatics, 3D genomics, Alzheimer's disease, Parkinson's disease, neurodegeneration, iPSC-derived neural cells

Techniques:
Capture C, ATAC-seq, ChIP-seq, RNA-seq, CRISPR/Cas9

Research summary:
Genetic studies have provided a wealth of variants associated with human complex traits, but are not able to pinpoint the underlying target genes and molecular mechanisms. We are interested in finding the target genes for several brain-related disorders, such as Alzheimer's, Parkinson's and other neurodegenerative disease. To do this, we use a combined wet-bench/bioinformatic approach, leveraging cutting-edge genomics and epigenetic techniques such as Capture C, ATAC-seq, ChIP-seq, and RNA-seq plus custom analysis pipelines and methods to perform a “variant-to-gene mapping” campaign for these disorders. We follow up candidate culprit variant-gene pairs by CRISPR/Cas9 editing and functional studies in appropriate cellular models of neurodegeneration, such as iPSC-derived neurons (cortical, dopaminergic, etc.), microglia, astrocytes, co-cultures and cerebral organoids (“brain in a dish”). Our ultimate goal is drug discovery for the identified target genes/molecular pathways, utilizing our cellular models of neurodegeneration for drug screens and leveraging system biology approaches.

Rotation projects:
Please contact Dr. Chesi to discuss possible rotation projects.

Selected Publications

Su C, Johnson ME, Torres A, Thomas RM, Manduchi E, Sharma P, Mehra P, Le Coz C, Leonard ME, Lu S, Hodge KM, Chesi A, Pippin J, Romberg N, Grant SFA, Wells AD: Mapping effector genes at lupus GWAS loci using promoter Capture-C in follicular helper T cells. Nature communications 11(1): 3294, Jul 2020.

Çalışkan Minal, Manduchi Elisabetta, Rao H Shanker, Segert Julian A, Beltrame Marcia Holsbach, Trizzino Marco, Park YoSon, Baker Samuel W, Chesi Alessandra, Johnson Matthew E, Hodge Kenyaita M, Leonard Michelle E, Loza Baoli, Xin Dong, Berrido Andrea M, Hand Nicholas J, Bauer Robert C, Wells Andrew D, Olthoff Kim M, Shaked Abraham, Rader Daniel J, Grant Struan F A, Brown Christopher D: Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver. American journal of human genetics 105(1): 89-107, Jul 2019.

Chesi Alessandra, Wagley Yadav, Johnson Matthew E, Manduchi Elisabetta, Su Chun, Lu Sumei, Leonard Michelle E, Hodge Kenyaita M, Pippin James A, Hankenson Kurt D, Wells Andrew D, Grant Struan F A: Genome-scale Capture C promoter interactions implicate effector genes at GWAS loci for bone mineral density. Nature communications 10(1): 1260, Mar 2019.

Chesi Alessandra, Mitchell Jonathan A, Kalkwarf Heidi J, Bradfield Jonathan P, Lappe Joan M, Cousminer Diana L, Roy Sani M, McCormack Shana E, Gilsanz Vicente, Oberfield Sharon E, Hakonarson Hakon, Shepherd John A, Kelly Andrea, Zemel Babette S, Grant Struan Fa: A Genomewide Association Study Identifies Two Sex-Specific Loci, at SPTB and IZUMO3, Influencing Pediatric Bone Mineral Density at Multiple Skeletal Sites. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32(6): 1274-1281, Jun 2017.

Medina-Gómez Carolina, Chesi Alessandra, Heppe Denise H M, Zemel Babette S, Yin Jia-Lian, Kalkwarf Heidi J, Hofman Albert, Lappe Joan M, Kelly Andrea, Kayser Manfred, Oberfield Sharon E, Gilsanz Vicente, Uitterlinden André G, Shepherd John A, Jaddoe Vincent W V, Grant Struan F A, Lao Oscar, Rivadeneira Fernando: BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures. Molecular biology and evolution 32(11): 2961-72, Nov 2015.

Chesi Alessandra, Mitchell Jonathan A, Kalkwarf Heidi J, Bradfield Jonathan P, Lappe Joan M, McCormack Shana E, Gilsanz Vicente, Oberfield Sharon E, Hakonarson Hakon, Shepherd John A, Kelly Andrea, Zemel Babette S, Grant Struan F A: A trans-ethnic genome-wide association study identifies gender-specific loci influencing pediatric aBMD and BMC at the distal radius. Human molecular genetics 24(17): 5053-9, Sep 2015.

Cirulli Elizabeth T, Lasseigne Brittany N, Petrovski Slavé, Sapp Peter C, Dion Patrick A, Leblond Claire S, Couthouis Julien, Lu Yi-Fan, Wang Quanli, Krueger Brian J, Ren Zhong, Keebler Jonathan, Han Yujun, Levy Shawn E, Boone Braden E, Wimbish Jack R, Waite Lindsay L, Jones Angela L, Carulli John P, Day-Williams Aaron G, Staropoli John F, Xin Winnie W, Chesi Alessandra, Raphael Alya R, McKenna-Yasek Diane, Cady Janet, Vianney de Jong J M B, Kenna Kevin P, Smith Bradley N, Topp Simon, Miller Jack, Gkazi Athina, Al-Chalabi Ammar, van den Berg Leonard H, Veldink Jan, Silani Vincenzo, Ticozzi Nicola, Shaw Christopher E, Baloh Robert H, Appel Stanley, Simpson Ericka, Lagier-Tourenne Clotilde, Pulst Stefan M, Gibson Summer, Trojanowski John Q, Elman Lauren, McCluskey Leo, Grossman Murray, Shneider Neil A, Chung Wendy K, Ravits John M, Glass Jonathan D, Sims Katherine B, Van Deerlin Vivianna M, Maniatis Tom, Hayes Sebastian D, Ordureau Alban, Swarup Sharan, Landers John, Baas Frank, Allen Andrew S, Bedlack Richard S, Harper J Wade, Gitler Aaron D, Rouleau Guy A, Brown Robert, Harms Matthew B, Cooper Gregory M, Harris Tim, Myers Richard M, Goldstein David B: Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways. Science 347(6229): 1436-41, Mar 2015.

Chesi Alessandra, Staahl Brett T, Jovičić Ana, Couthouis Julien, Fasolino Maria, Raphael Alya R, Yamazaki Tomohiro, Elias Laura, Polak Meraida, Kelly Crystal, Williams Kelly L, Fifita Jennifer A, Maragakis Nicholas J, Nicholson Garth A, King Oliver D, Reed Robin, Crabtree Gerald R, Blair Ian P, Glass Jonathan D, Gitler Aaron D: Exome sequencing to identify de novo mutations in sporadic ALS trios. Nature neuroscience 16(7): 851-5, Jul 2013.

Chesi Alessandra, Kilaru Austin, Fang Xiaodong, Cooper Antony A, Gitler Aaron D: The role of the Parkinson's disease gene PARK9 in essential cellular pathways and the manganese homeostasis network in yeast. PloS one 7(3): e34178, March 2012.

Gitler Aaron D*, Chesi Alessandra*, Geddie Melissa L*, Strathearn Katherine E, Hamamichi Shusei, Hill Kathryn J, Caldwell Kim A, Caldwell Guy A, Cooper Antony A, Rochet Jean-Christophe, Lindquist Susan: Alpha-synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity. Nature genetics 41(3): 308-15, Mar 2009 Notes: *contributed equally.

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Last updated: 04/12/2021
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