The Krauss lab is interested in how cell-cell adhesion and signal transduction pathways interact to regulate cell fate during embryonic developmental and adult tissue regeneration. We take a multidisciplinary approach that includes mouse and human genetics, cell biology, and biochemistry to address these broad questions with several model systems. One major focus is the role of cadherins as niche factors for skeletal muscle stem cells. We also study Hedgehog pathway signaling in early midline patterning and how defects in this process result in the common birth defect holoprosencephaly.
The skeletal muscle stem cell niche
Satellite cells (SCs) are adult skeletal muscle stem cells located between the myofiber and its surrounding basal lamina, and they are the source of skeletal muscle’s remarkable regenerative properties. SCs exist in a largely quiescent state in adult mice. However, upon muscle injury they are activated to proliferate and produce the myoblasts that will ultimately differentiate to form new myofibers; they also self-renew to replenish the muscle stem cell compartment. Quiescence is promoted by the SC niche, including the myofiber itself. Using a combination of conditional mouse mutants and cell biological analyses, we have shown that classical cadherins are components of the niche, required cell-autonomously by both the fiber and SC. We are continuing these studies with additional components of cadherin-based cell-cell junctions. We are also interested in the fundamental question of how the myofiber constructs and maintains a niche for SCs, as SCs are small, polarized, and mononuclear cells, whereas myofibers are large, non-polarized, and multinucleated cells. SCs and myofibers are in direct cell-cell contact (with cadherins present precisely where the two cells touch) but this junction represents a very small amount of the total myofiber cell surface. We are studying this question with a combination of in vivo and ex vivo approaches.
Modeling holoprosencephaly in the mouse
Holoprosencephaly (HPE) is a common developmental defect caused by failure to define the midline of the forebrain and/or midface. HPE is associated with heterozygous mutations in Nodal and Hedgehog (Hh) pathway components, but clinical presentation is highly variable, and many mutation carriers are unaffected. It is therefore thought that such mutations interact with more common modifiers, genetic and/or environmental, to produce severe patterning defects. Modifiers are difficult to identify, as their effects are context-dependent and occur within the complex genetic and environmental landscapes that characterize human populations. This has made a full understanding of HPE etiology challenging. We have developed mouse models for HPE that shed light on its complex etiology. Our studies with mouse lines carrying Hh pathway mutations on appropriate genetic backgrounds have led to identification of both genetic and environmental modifiers that synergize with the mutations to produce a spectrum of HPE phenotypes. These models favor a scenario in which multiple modifying influences—both genetic and environmental, sensitizing and protective—interact with bona fide HPE mutations to grade phenotypic outcomes. Despite the complex interplay of HPE risk factors, our findings have helped establish some clear concepts in HPE etiology.
Featured Recent Publications
Krauss, R.S., M.D. Shapiro, P.L. Koch, G. Kardon, and D.D.W. Cornelison. (2019). Science at Sundance. Science, 363:1270-1274. http://science.sciencemag.org/content/363/6433/1270
Goel, A.J., M.K. Rieder, H.H. Arnold, G.L. Radice, and R.S. Krauss. (2017). Niche cadherins control the quiescence-to-activation transition in muscle stem cells. Cell Reports, 21:2236-2250.
Hong, M., K. Srivastava, S. Kim, B.L. Allen, D.J. Leahy, P. Hu, E. Roessler, R.S. Krauss* and M. Muenke*. (2017). BOC is a modifier gene in holoprosencephaly. Hum Mutat., 38:1464-1470.
Meet the Team
Rob is interested in how cell adhesion and signal transduction interact to make stuff happen in developing embryos and regenerating tissues. His students and postdocs have been making him look good for a long time.
Allison is a third-year PhD student interested in understanding how the muscle stem cell niche is constructed and maintained. When she isn’t in lab, she spends her time enjoying the best parts of NYC – the food, the parks, and the Broadway shows.
Research Assistant Professor
Mingi is a Research Assistant Professor interested in gene-environment interactions during development and how they contribute to the etiology of birth defects. Living things thrive around her, including the plants in the lab and her wonderful cat.
Vivian is a postdoc interested in regulation of Shh signaling during early central nervous system development. Outside the lab, her favorite pastime is watching live sporting events in NYC, especially the US Open.
Maggie is a second-year PhD student studying how various catenin proteins regulate satellite cells in quiescence and in response to muscle injury. When not in lab, she enjoys sampling the great culinary treats in New York City, drinking too much coffee, and admiring all the dogs playing in central park.
Zoë is a research assistant working on the Hedgehog coreceptor Boc. She plans to obtain a PhD in Biochemistry. Outside the lab she is a special effects makeup artist for film and stage, and a baker.
Gyu-un Bae Associate Professor • Sookmyung Womens University • Seoul, Republic of Korea
Francesca Cole Associate Professor • Molecular Carcinogenesis • MD Anderson Cancer Center • Smithville, TX
Iris Cheng City Research Scientist • New York City Department of Health
Daisuke Chihara Postdoctoral Fellow • Skirball Institute • New York University • New York, NY
Jessica Feinleib Assistant Professor • Anesthesiology • Yale School of Medicine • New Haven, CT
Aviva Goel • Maternity break
Guoying Jiang Senior Staff Scientist • Pharma Technical Development • Genentech • South San Francisco, CA
Giselle Joseph Postdoctoral Fellow • Novartis Institute for Biomedical Research • Cambridge, MA
Jong-Sun Kang Professor • Samsung Biomedical Research Institute • Sungkyunkwan University School of Medicine • Suwon, Republic of Korea
Sarah Knox Associate Professor • Cell and Tissue Biology • UC San Francisco
Youl-Nam Lee BioGemex Ltd. • Sung Nam, Republic of Korea
Min Lu Senior Scientist • Agios, Inc. • Cambridge, MA
Philip Mulieri Danbury Orthopedics • Danbury, CT
Marysia-Kolbe Rieder MS in Genetic Counseling student • Icahn School of Medicine at Mount Sinai • New York, NY
Anthony Romer Scientist • Sigilon Therapeutics • Cambridge, MA
Karen Schachter Scientist • Stem Cell Development • Novo Nordisk • Denmark
Dario Sirabella Associate Research Scientist • Stem Cell Core Columbia University Medical Center • New York, NY
Giichi Takaesu Associate Professor • University of the Ryukyus • Okinawa, Japan
Jaw-Ji Yang Professor • Chung Shan Medical University • Taichung, Taiwan
Wei Zhang Postdoctoral Fellow • Skirball Institute • New York University • New York, NY
Krauss lab at the 2018 departmental retreat
Giselle’s defense party!
Rob attends the Sundance Film Festival and reviews films for Science
Aviva’s defense party!
The secret is out
Allison and Maggie take some time out from the 2018 Muscle Stem Cell Conference
Krauss lab at the March for Science
The chick lab with an egg
RK and ST – separated at birth?
Professor, Cell, Developmental, and Regenerative Biology