Faculty

Ana G Cristancho, MD, PhD

faculty photo
Assistant Professor of Neurology
Department: Neurology
Graduate Group Affiliations

Contact information
Colket Translational Research Building, 6020
3501 Civic Center Blvd
Philadelphia, PA 19104
Education:
BS (Biology and Philosophy)
University of Miami, 2004.
PhD (Cell and Molecular Biology)
University of Pennsylvania, 2011.
MD
University of Pennsylvania, 2013.
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Description of Research Expertise

Research Interests:
The Cristancho lab is interested in understanding the epigenetic mechanisms driving long-term neurodevelopmental disabilities from acquired prenatal and perinatal brain injury. We posit that even in the setting of little cell death, epigenome disruption during critical stages of early brain development persistently alters brain maturation and function.

Keywords:
prenatal brain injury, epigenetics, neurodevelopmental disorders, multi-omics, behavior, translational, hypoxia

Research Details:
Prenatal and perinatal brain injuries, including prenatal hypoxia, are among the most common causes of neurodevelopmental disabilities worldwide, ranging from developmental delays, autism, epilepsy, cerebral palsy, and learning disabilities. However, despite their prevalence, we have almost no directed therapies for these disorders. Part of the challenge is that these injuries are variable in what causes them, how long the insult lasts, and lead to a wide variety of disabilities in affected children.

To study these questions, we use a combination of animal and cell culture models and take advantage of multi-omic approaches to garner a multi-dimensional understanding of these complex brain injuries on different cell types. We then use physiologic, behavioral, and imaging outputs to link changes in the epigenetic signature to functional outcomes to determine which changes to the epigenome are important for modulating the severity of neurodevelopmental deficits after developmental brain injury.

We are currently focusing on a model of transient prenatal hypoxia, where we found there is little early cell death, but there are persistent deficits in adult animals (decreased seizure threshold and other behavior anomalies). Using single nucleus RNA-seq and ATAC-seq, we are currently unraveling the cell type-specific dynamics that drive these persistent functional deficits long after the insult has occurred.

Rotation Projects:
Please contact us for a discussion of possible rotation projects.

Selected Publications

Guez-Barber D, Eisch AJ, Cristancho AG. : Developmental brain injury and social determinants of health: opportunities to combine preclinical models for mechanistic insights into recovery. Developmental Neuroscience April 2023 Notes: doi: 10.1159/000530745.

Means M, Whitehead MT, Borst AJ: Neonatal Medullary Venous Thrombosis and Hemorrhage from Protein C Deficiency. Neuropediatrics March 2023.

Cristancho AG*, Tulina N*, Brown, A, Anton L, Barila G, Elovitz MA. : Intrauterine inflammation leads to some sex and age-specific behavior and molecular differences in mice. Int J Mol Sci 24, December 2022 Notes: doi: 10.3390/ijms24010032.

Gadra EC, Cristancho AG: A Simplified Paradigm of Late Gestation Transient Prenatal Hypoxia to Investigate Functional and Structural Outcomes from a Developmental Hypoxic Insult. Bio-protocol October 2022 Notes: DOI: 10.21769/BioProtoc.4519.

Adutwum M, Hurst A, Mirzaa G, Kushner JD, Rogers C, Khalek N, Cristancho AG, Burrill N, Seifert ME, Scarano MI, Schnur RE, Slavotinek A. : Six new cases of CRB2-related syndrome and a review of clinical findings in 28 reported patients. Clin Genet. September 2022 Notes: doi: 10.1111/cge.14222.

Cristancho A, Gadra E, Samba I, Zhao C, Ouyang M, Magnitsky S, Huang H, Viaene A, Anderson S, Marsh E. : Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia. Developmental Neuroscience 44: 246-265, March 2022 Notes: doi: 10.1159/000524045.

Abdelmoumen I, Jimenez S, Valencia I, Melvin J, Legido A, Diaz-Diaz MM, Griffith C, Massingham LJ, Yelton M, Rodríguez-Hernández J, Schnur RE, Walsh LE, Cristancho AG, Bergqvist CA, McWalter K, Mathieson I, Belbin GM, Kenny EE, Ortiz-Gonzalez XR, Schneider MC.: Boricua Founder Variant in FRRS1L Causes Epileptic Encephalopathy With Hyperkinetic Movements. J Child Neurol September 2021.

Joseph DJ, Von Deimling M, Hasegawa Y, Cristancho AG, Risbud R, McCoy AJ, Marsh ED.: Protocol for isolating young adult parvalbumin interneurons from the mouse brain for extraction of high-quality RNA. STAR Protoc 2: 100714, Aug 2021.

Yardeni T, Cristancho AG, McCoy AJ, Schaefer PM, McManus MJ, Marsh ED, Wallace DC.: An mtDNA mutant mouse demonstrates that mitochondrial deficiency can result in autism endophenotypes. Proc Natl Acad Sci U S A 118: e2021429118, Feb 2021.

Fitzgerald MP, Kaufman MC, Massey SL, Fridinger S, Prelack M, Ellis C, Ortiz-Gonzalez X, Fried LE, DiGiovine MP; CHOP Pediatric Epilepsy Program Collaborative, Melamed S, Malcolm M, Banwell B, Stephenson D, Witzman SM, Gonzalez A, Dlugos D, Kessler SK, Goldberg EM, Abend NS, Helbig I.: Assessing seizure burden in pediatric epilepsy using an electronic medical record-based tool through a common data element approach. Epilepsia 2021.

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Last updated: 07/30/2023
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