Faculty

Santhosh Girirajan

Professor of Genomics
Professor of Anthropology
Department Head of Biochemistry and Molecular Biology
Huck Co-Hire with Eberly College of Science

205A Huck Life Sciences
University Park, PA

Email sxg47@psu.edu
Phone 814-865-0674

Overview

Understanding the genetic basis of neurodevelopmental disorders.

Areas of Expertise

Copy Number Variation Keyphrases
Genetics Biochemistry, Genetics and Molecular Biology
Autism Keyphrases
Genomics Biochemistry, Genetics and Molecular Biology
Smith-Magenis Syndrome Biochemistry, Genetics and Molecular Biology
Intellectual Disability Biochemistry, Genetics and Molecular Biology
Smith-Magenis Syndrome Keyphrases
Copy-Number Variation Biochemistry, Genetics and Molecular Biology

Functional impact of genetic background on variable expressivity in neurodevelopmental disorders
Jiawan Sun, Serena Noss, Corrine Smolen, Venkata Hemanjani Bhavana, Deepro Banerjee, Maitreya Das, Belinda Giardine, Anisha Prabhu, David J. Amor, Kate Pope, Paul J. Lockhart, Santhosh Girirajan, Dec 2026, In: Nature communications
Date: Dec 2026

Protocol for identifying genetic modifiers of phenotypes in individuals with disease-associated variants
Corrine Smolen, Matthew Jensen, Santhosh Girirajan, Jun 19 2026, In: STAR Protocols
Date: Jun 19 2026

Genetic modifiers and ascertainment drive variable expressivity of complex disorders
Matthew Jensen, Corrine Smolen, Anastasia Tyryshkina, Lucilla Pizzo, Jiawan Sun, Serena Noss, Deepro Banerjee, Matthew Oetjens, Hermela Shimelis, Cora M. Taylor, Vijay Kumar Pounraja, Hyebin Song, Laura Rohan, Emily Huber, Laila El Khattabi, Ingrid van de Laar, Rafik Tadros, Connie R. Bezzina, Marjo..., Dec 11 2025, In: Cell
Date: Dec 11 2025

Discovery of obesity genes through cross-ancestry analysis
Deepro Banerjee, Santhosh Girirajan, Dec 2025, In: Nature communications
Date: Dec 2025

Expectations for papers performing Mendelian randomization analyses
Scott M. Williams, Hua Tang, Gregory M. Cooper, Anne O’Donnell-Luria, Santhosh Girirajan, Aimée M. Dudley, Anne Goriely, Zoltán Kutalik, Xiaofeng Zhu, Giorgio Sirugo, Michael P. Epstein, 2025, In: PLoS genetics
Date: 2025

Whole genome sequencing analysis identifies sex differences of familial pattern contributing to phenotypic diversity in autism
Soo Whee Kim, Hyeji Lee, Da Yea Song, Gang Hee Lee, Jungeun Ji, Jung Woo Park, Jae Hyun Han, Jee Won Lee, Hee Jung Byun, Ji Hyun Son, Ye Rim Kim, Yoojeong Lee, Jaewon Kim, Ashish Jung, Junehawk Lee, Eunha Kim, So Hyun Kim, Jeong Ho Lee, F. Kyle Satterstrom, Santhosh Girirajan, Anders D. Børglum, Ja..., Dec 2024, In: Genome Medicine
Date: Dec 2024

Flynotyper 2.0
Johnathan Ray, Deepro Banerjee, Qingyu Wang, Santhosh Girirajan, Nov 2024, In: G3: Genes, Genomes, Genetics
Date: Nov 2024

Strategies for dissecting the complexity of neurodevelopmental disorders
Jiawan Sun, Serena Noss, Deepro Banerjee, Maitreya Das, Santhosh Girirajan, 2023, In: Trends in Genetics
Date: 2023

Transcriptome signatures of the medial prefrontal cortex underlying GABAergic control of resilience to chronic stress exposure
Meiyu Shao, Julia Botvinov, Deepro Banerjee, Santhosh Girirajan, Bernhard Lüscher, 2024, In: Molecular Psychiatry
Date: 2024

Assortative mating and parental genetic relatedness contribute to the pathogenicity of variably expressive variants
Corrine Smolen, Matthew Jensen, Lisa Dyer, Lucilla Pizzo, Anastasia Tyryshkina, Deepro Banerjee, Laura Rohan, Emily Huber, Laila El Khattabi, Paolo Prontera, Jean Hubert Caberg, Anke Van Dijck, Charles Schwartz, Laurence Faivre, Patrick Callier, Anne Laure Mosca-Boidron, Mathilde Lefebvre, Kate Pope..., Dec 7 2023, In: American Journal of Human Genetics
Date: Dec 7 2023

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Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
Brian J. O ’ Roak, Laura Vives, Santhosh Girirajan, Emre Karakoc, Niklas Krumm, Bradley P. Coe, Roie Levy, Arthur Ko, Choli Lee, Joshua D. Smith, Emily H. Turner, Ian B. Stanaway, Benjamin Vernot, Maika Malig, Carl Baker, Joshua M. Akey, Elhanan Borenstein, Mark J. Rieder, Deborah A. Nickerson, Ra..., May 9 2012, In: Nature
Citations: 1,809

A copy number variation morbidity map of developmental delay
Gregory M. Cooper, Bradley P. Coe, Santhosh Girirajan, Jill A. Rosenfeld, Tiffany H. Vu, Carl Baker, Charles Williams, Heather Stalker, Rizwan Hamid, Vickie Hannig, Hoda Abdel-Hamid, Patricia Bader, Elizabeth McCracken, Dmitriy Niyazov, Kathleen Leppig, Heidi Thiese, Marybeth Hummel, Nora Alexander,..., Sep 2011, In: Nature Genetics
Citations: 1,113

Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
Brian J. O'Roak, Pelagia Deriziotis, Choli Lee, Laura Vives, Jerrod J. Schwartz, Santhosh Girirajan, Emre Karakoc, Alexandra P. MacKenzie, Sarah B. Ng, Carl Baker, Mark J. Rieder, Deborah A. Nickerson, Raphael Bernier, Simon E. Fisher, Jay Shendure, Evan E. Eichler, Jun 2011, In: Nature Genetics
Citations: 978

A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay
Santhosh Girirajan, Jill A. Rosenfeld, Gregory M. Cooper, Francesca Antonacci, Priscillia Siswara, Andy Itsara, Laura Vives, Tom Walsh, Shane E. McCarthy, Carl Baker, Heather C. Mefford, Jeffrey M. Kidd, Sharon R. Browning, Brian L. Browning, Diane E. Dickel, Deborah L. Levy, Blake C. Ballif, Kathry..., Mar 2010, In: Nature Genetics
Citations: 517

Population analysis of large copy number variants and hotspots of human genetic disease
Andy Itsara, Gregory M. Cooper, Carl Baker, Santhosh Girirajan, Jun Li, Devin Absher, Ronald M. Krauss, Richard M. Myers, Paul M. Ridker, Daniel I. Chasman, Heather Mefford, Phyllis Ying, Deborah A. Nickerson, Eva E. Eichler, Aug 8 2008, In: American Journal of Human Genetics
Citations: 502

Phenotypic heterogeneity of genomic disorders and rare copy-number variants
Santhosh Girirajan, Jill A. Rosenfeld, Bradley P. Coe, Sumit Parikh, Neil Friedman, Amy Goldstein, Robyn A. Filipink, Juliann S. McConnell, Brad Angle, Wendy S. Meschino, Marjan M. Nezarati, Alexander Asamoah, Kelly E. Jackson, Gordon C. Gowans, Judith A. Martin, Erin P. Carmany, David W. Stockton, ..., Oct 4 2012, In: New England Journal of Medicine
Citations: 492

De novo pathogenic SCN8A mutation identified by whole-genome sequencing of a family quartet affected by infantile epileptic encephalopathy and SUDEP
Krishna R. Veeramah, Janelle E. O'Brien, Miriam H. Meisler, Xiaoyang Cheng, Sulayman D. Dib-Hajj, Stephen G. Waxman, Dinesh Talwar, Santhosh Girirajan, Evan E. Eichler, Linda L. Restifo, Robert P. Erickson, Michael F. Hammer, Mar 9 2012, In: American Journal of Human Genetics
Citations: 389

Human copy number variation and complex genetic disease
Santhosh Girirajan, Catarina D. Campbell, Evan E. Eichler, 2011, In: Annual review of genetics
Citations: 307

Relative burden of large CNVs on a range of neurodevelopmental phenotypes
Santhosh Girirajan, Zoran Brkanac, Bradley P. Coe, Carl Baker, Laura Vives, Tiffany H. Vu, Neil Shafer, Raphael Bernier, Giovanni B. Ferrero, Margherita Silengo, Stephen T. Warren, Carlos S. Moreno, Marco Fichera, Corrado Romano, Wendy H. Raskind, Evan E. Eichler, Nov 2011, In: PLoS genetics
Citations: 267

Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder
Santhosh Girirajan, Megan Y. Dennis, Carl Baker, Maika Malig, Bradley P. Coe, Catarina D. Campbell, Kenneth Mark, Tiffany H. Vu, Can Alkan, Ze Cheng, Leslie G. Biesecker, Raphael Bernier, Evan E. Eichler, Feb 7 2013, In: American Journal of Human Genetics
Citations: 261

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Centers & Institutes

Researchers have developed a new framework to study the functional impact of genetic background on the expression and severity of neurodevelopmental features associated with a deletion of a portion of chromosome 16. The research team used induced pluripotent stem cells (iPSC) derived from patients with the deletion, their families and a healthy donor that they differentiated into different types of neuronal cells — image shows immunostained iPSC-derived neurons on the left and iPSC-derived neural progenitor cells on the right — to study how interactions among a patient’s entire genetic architecture and the deletion help determine the features that the individual will manifest. Credit: Girirajan Laboratory / Penn State. Creative Commons

May 05, 2026

How can the same genetic mutation lead to different clinical outcomes?

April 20, 2026

Sun awarded Robert T. Simpson Graduate Student Award for Innovative Research.

Santhosh Girirajan speaking to residents at the Village at Penn State during Brain Awareness Week.

March 26, 2026

Community Q&A: Brain health and neuroscience research

Paul Babitzke, Stanley R. Person Professor of Molecular Biology, Don Bryant Chair in Microbial Physiology in the Department of Biochemistry and Molecular Biology, and director of the Center for RNA Molecular Biology at Penn State, presenting at the RNA Symposium. Credit: Penn State. Creative Commons

November 14, 2025

Penn State molecular biologist named Don Bryant Chair in Microbial Physiology

November 01, 2025

A Multi-Ancestry Analysis Reveals Novel Obesity-Related Genes

October 31, 2025

Massive cross-ancestry study explains why obesity risks differ around the world

$A new study involving about 850,000 adults across six continental ancestries, has identified 13 genes associated with obesity across ancestries. While eight of these genes had been found in previous studies, five were identified for the first time, having no previous links to obesity. The colors of the DNA helix in the image represent ancestral difference in genetic background around the world. The black figures represent people who do not carry gene mutations found to be associated with obesity while the red figures carry them. The fraction of red and black figures highlights the differences in genetic mutations across the world. Credit: Deepro Banerjee, Girirajan Laboratory / Penn State. Creative Commons$

October 30, 2025

Genes associated with obesity shared across ancestries, researchers find

October 07, 2025

1 gene, 1 disease no more – acknowledging the full complexity of genetics could improve and personalize medicine

New research helps explain why disease-associated genetic variants can lead to variable clinical outcomes, influenced both by the patterns of secondary variants, or genetic background, and by how cohorts of individuals in a study are ascertained. In a family, shown on left, secondary variants can influence the severity of clinical outcomes, which is indicated by intensity of blue shading, or which features are present between a parent and a child that both carry the primary variant. However, this relationship between secondary and primary variants is different if the primary variant was discovered in a biobank that includes mostly healthy individuals, in the middle, or people identified for a shared clinical feature, on right. Credit: Corrine Smolen/Girirajan Laboratory / Penn State. Creative Commons

October 07, 2025

Background genetic variants influence clinical features in complex disorders

Graduate student Chad Smies and postdoctoral scholar Jiyeon “Joan” Baek manipulate a solution that will be used to visualize protein expression in the mouse brain. Credit: Michelle Bixby / Penn State. Creative Commons

July 14, 2025

The breadth of the brain

Yongsoo Kim, associate professor of neural and behavioral sciences at the Penn State College of Medicine, is leading a new five-year, $17.9 million grant from the National Institutes of Health's National Institute of Mental Health. Credit: Jason Plotkin / Penn State. Creative Commons

January 23, 2025

$17.9M NIH grant to research neurodevelopment disorders

New research finds sex-specific regions of the brain can relieve the detrimental effects of chronic stress in male and female mice. Left: Schematic showing a cortical microcircuit with three types of interneurons expressing somatostatin (SST), parvalbumin (PV) or vasointestinal peptide (VIP) and their distinct patterns of innervation of glutamatergic output neurons (PNs), with thin lines representing axons that send chemical signals and the thicker lines of PNs representing dendrites that receive information. There is selective innervation of the distal ends of PN dendrites by axons of SST neurons. Right: Increased activity of SST neurons by genetically induced disinhibition, on top right, or by chemogenetic activation of SST neurons in the medial prefrontal cortex, on bottom right, leads to stress resilience and facilitates the reversal of the detrimental behavioral effects of stress exposure in male but not female mice. Credit: Bernhard Lüscher / Penn State. Creative Commons

December 16, 2024