Lindsey Barske

Lindsey Barske, PhD


  • Member, Division of Human Genetics
  • Member, Division of Developmental Biology
  • Assistant Professor, UC Department of Pediatrics

About

Biography

"Our real teacher has been and still is the embryo, who is, incidentally, the only teacher who is always right."
                                                                                                                               – Viktor Hamburger

The process of building a new individual from a fertilized egg is, to my mind, one of the most intricate and beautifully orchestrated affairs in the known world. We understand just a fraction of the myriad steps that must unfold sequentially for embryogenesis to be successful, and for those few, we still see them through a glass, darkly. Each time developmental biologists unlock another secret of the embryo, many others, once hidden, come into view. Still, by studying how embryonic cells come to adopt their final fates and how organs are positioned, built and joined together in early life, we can better understand how things have gone awry in children with congenital defects and how best to treat them. We also provide a reference for comparison for replacement organs that are being built through regenerative medicine efforts.

My group studies the genetic control of skeletal form in the head: how genes interact to determine where and when skeletal progenitor cells begin to differentiate into cartilage or bone in the head of the embryo. We use zebrafish and mouse models and state-of-the-art genetic engineering and imaging methods to dissect the individual roles of our genes of interest in building the skull. One of our notable discoveries was the identification of genes that make the upper jaw different from the lower jaw – in fish mutant for these genes, the upper jaw has transformed into a mirror image duplicate of the lower jaw. We are also very interested in the genetic pathways that prevent the early differentiation of certain populations of skeletal progenitor cells. Mutations in these genes can lead to precocious or ectopic differentiation and may deplete stem cell populations needed to make later-forming cell types or to maintain adult bones.

Importantly for human health, we hypothesize that this type of precocious differentiation is a common cause contributing to a number of craniofacial anomalies, including cleft palate, maxillary hypoplasia, premature fusion of the cranial sutures (craniosynostosis), and middle ear bone abnormalities. By investigating how genes work in concert to sculpt the skull as it forms, we hope to improve intervention paradigms for pediatric patients and to better calculate recurrence risks for their families.

I have more than 15 years of experience in genetics and developmental biology research. I grew up in New England and then fled its long winters for sunny Southern California for my undergraduate degree at Pomona College in Los Angeles. After three post-baccalaureate research assistantships at a field station in Alaska, a cancer epigenetics lab, and a developmental neurobiology lab, I entered the PhD program in Developmental Biology at Duke University in 2006 and completed my degree in 2011. I then held a postdoctoral fellow position at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at University of Southern California from 2012-2018. In the summer of 2018, I moved back across the country and opened my own lab at the Cincinnati Children’s Hospital Medical Center.

Throughout my career, I have received multiple grants and honors, including the Chi-Bin Chien award from the International Zebrafish Society in 2018 and the K99/R00 Pathway to Independence award from the National Institute of Dental and Craniofacial Research in 2016. My research has been published in many respected journals, such as Nature, Developmental Cell, PNAS, Development, Developmental Biology, PLOS Genetics, and Nature Communications.

To balance all of the time spent in the lab, I row on the Licking River, bike, climb mountains and go camping with my family in national parks as often as I can.

BA: Department of Biology, Pomona College, Claremont, CA, 2000-2004.

PhD: Department of Cell Biology, Duke University School of Medicine, Durham, NC, 2006-2012.

Postdoctoral Training: Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, CA, 2012-2018.

Interests

Craniofacial development; genetic engineering

Research Areas

Human Genetics

Publications

Nuclear receptor Nr5a2 promotes diverse connective tissue fates in the jaw. Chen, H; Barske, L; Talbot, JC; Dinwoodie, OM; Roberts, RR; Farmer, DT; Jimenez, C; Merrill, AE; Tucker, AS; Crump, JG. Developmental Cell. 2023; 58:461-473.e7.

Biased precursor ingression underlies the center-to-pole pattern of male sex determination in mouse. Bunce, C; Barske, L; Zhang, G; Capel, B. Development (Cambridge). 2023; 150.

Control of cranial ectomesenchyme fate by Nr2f nuclear receptors. Okeke, C; Paulding, D; Riedel, A; Paudel, S; Phelan, C; Teng, CS; Barske, L. Development (Cambridge). 2022; 149.

Patterning of cartilaginous condensations in the developing facial skeleton. Paudel, S; Gjorcheska, S; Bump, P; Barske, L. Developmental Biology. 2022; 486:44-55.

Intrahepatic cholangiocyte regeneration from an Fgf-dependent extrahepatic progenitor niche in a zebrafish model of Alagille Syndrome. Zhao, C; Lancman, JJ; Yang, Y; Gates, KP; Cao, D; Barske, L; Matalonga, J; Pan, X; He, J; Graves, A; Huisken, J; Chen, C; Dong, P. Hepatology. 2022; 75:567-583.

Evolution of vertebrate gill covers via shifts in an ancient Pou3f3 enhancer. Barske, L; Fabian, P; Hirschberger, C; Jandzik, D; Square, T; Xu, P; Nelson, N; Yu, HV; Medeiros, DM; Gillis, JA; Crump, JG. Proceedings of the National Academy of Sciences of USA. 2020; 117:24876-24884.

Zebrafish prrx1a mutants have normal hearts. Tessadori, F; de Bakker, DE M; Barske, L; Nelson, N; Algra, HA; Willekers, S; Nichols, JT; Crump, JG; Bakkers, J. Nature. 2020; 585:E14-E16.