Irene Kaplow
Assistant Professor
To start in August 2024
Address:
Department of Biological Sciences
Carnegie Mellon University
4400 Fifth Avenue
Pittsburgh, PA 15213
Education
Postdoctoral Appointment, Carnegie Mellon University
Research
I am interested in deciphering the transcriptional regulatory mechanisms underlying the evolution of phenotypes that differ between mammals. This interest is motivated by previous work indicating that protein-coding differences between mammals cannot fully explain the evolution of many mammalian phenotypes, such as brain size and longevity, suggesting that these phenotypes have evolved in large part due to differences between species in the activity of enhancers, genomic regions that regulate transcription, which are often tissue-specific.
To pursue this interest, I led the development of a framework for associating differences between species in enhancer activity in a tissue of interest with the evolution of a phenotype of that tissue. This work led me to join the Zoonomia Consortium, a consortium of evolutionary biologists who are sequencing and analyzing hundreds of mammalian genomes, through which I have started collaborations with experts in multiple mammalian phenotypes. I aim to use these collaborations to apply my framework to a wide range of phenotypes while simultaneously developing computational methods to improve my framework and designing experiments to validate hypotheses generated by my work.
Publications
Christmass MJ*, Kaplow IM*, Genereux DP, Dong MX, Hughes GM, Li X, Sullivan PF, Hindle AG, Andrews G, Armstrong JC, Bianchi M, Breit AM, Diekhans M, Fanter C, Foley NM, Goodman DB, Goodman L, Keough KC, Kirilenko B, Kowalczyk A, Lawless C, Lind AL, Meadows JRS, Moreira L, Redlich RW, Ryan L, Swofford R, Valenzuela A, Wagner F, Wallerman O, Brown AR, Damas J, Fan K, Gimshaw J, Johnson J, Kozyrev SV, Lawler AJ, Marinescu VD, Morril KM, Osmanski A, Paulat NS, Phan BN, Reilly SK, Schäffer DE, Steiner C, Supple MA, Wilder AP, Wirthlin ME, Xue JR, Zoonomia Consortium, Birren BW, Gazal S, Hubley RM, Koepfli KP, Marques-Bonet T, Meyer WK, Nweeia M, Sabeti PC, Shapiro B, Smit AFA, Springer M, Teeling E, Weng Z, Hiller M, Levesque DL, Lewin HA, Murphy WJ, Navarro A, Paten B, Pollard KS, Ray DA, Ruf I, Ryder OA, Pfenning AR, Lindblad-Toh K#, Karlsson EK#. Evolutionary constraint and innovation across hundreds of placental mammals. Science, 2023. PubMed
Kaplow IM*#, Lawler AJ*, Schäffer DE*, Srinivasan C, Sestili HH, Wirthlin ME, Phan BN, Prasad K, Brown AR, Zhang X, Foley K, Genereux DP, Zoonomia Consortium, Karlsson EK, Lindblad-Toh K, Meyer WK, Pfenning AR#. Relating enhancer genetic variation across mammals to complex phenotypes using machine learning. Science, 2023. PubMed
Kaplow IM#, Banerjee A, Foo CS#. Neural network modeling of differential binding between wild-type and mutant CTCF reveals putative binding preferences for zinc fingers 1–2. BMC Genomics, 2022. PubMed
Kaplow IM#, Schäffer DE, Wirthlin ME, Lawler AJ, Brown AR, Kleyman M, Pfenning AR#. Inferring mammalian tissue-specific regulatory conservation by predicting tissue-specific differences in open chromatin. BMC Genomics, 2022. PubMed
Lawler AJ, Ramamurthy E, Brown AR, Shin N, Kim Y, Toong N, Kaplow IM, Wirthlin M, Zhang X, Fox G, Wade K, He J, Ozturk BE, Byrne LC, Stauffer WR, Fish KN, Pfenning AR. Machine learning sequence prioritization for cell type-specific enhancer design. Elife, 2022. PubMed
Srinivasan C*, Phan BN*, Lawler AJ, Ramamurthy E, Kleyman M, Brown AR, Kaplow IM, Wirthlin ME, Pfenning AR. Addiction-associated genetic variants implicate brain cell type- and region-specific cis-regulatory elements in addiction neurobiology. Journal of Neuroscience, 2021. PubMed
Spix TA, Nanivadekar S, Toong N, Kaplow IM, Isett BR, Goksen Y, Pfenning AR, Gittis AH. Population-Specific Neuromodulation Prolongs Therapeutic Benefits of Deep Brain Stimulation. Science, 2021. PubMed
Kaplow IM, MacIsaac JL*, Mah SM*, McEwen LM, Kobor MS, Fraser HB. A pooling-based approach to mapping genetic variants associated with DNA methylation.. Genome Research, 2015. PubMed