Rudolf Jaenisch, MD

Member, Whitehead Institute Professor of Biology, MIT 617.258.5189 phone kemske@wi.mit.edu

“What makes a given cell a given cell—what makes a liver cell a liver cell versus a brain cell versus an embryonic cell?” asks Rudolf Jaenisch. “We want to understand this in molecular terms, and we are using this information to convert one cell type into another.”

Jaenisch, a Whitehead Founding Member, focuses on understanding epigenetic regulation of gene expression (the biological mechanisms that affect how genetic information is converted into cell structures but that don’t alter the genes in the process). Most recently, this work has led to major advances in our understanding of embryonic stem cells and “induced pluripotent stem” (IPS) cells, which appear identical to embryonic stem cells but can be created from adult cells without using an egg.

In 2007, the Jaenisch lab was one of three labs worldwide that reported successfully taking cells from mouse tails and reprogramming them into IPS cells, by over-expressing four master gene regulators. Later that year, the lab followed up by further manipulating IPS cells to treat sickle-cell anemia in mice, the first proof in principle of therapeutic use of such cells. In 2008, the lab reported that neurons derived from IPS cells successfully integrated into fetal mouse brains and reduced symptoms in a Parkinson's disease rat model. In another experiment, researchers demonstrated that fully mature, differentiated mouse B cells can be reprogrammed to IPS cells.

Researchers are now studying ways to optimize the creation of IPS cells, including finding alternatives to the potentially cancer-causing retroviruses used to transform the adult cells into IPS cells.

In the long run, IPS cells offer major promise for use in regenerative medicine, potentially supporting the growth of healthy cells and tissues derived from a patient’s own cells. Closer in time, the cells will allow scientists to transfer complex human diseases into Petri dishes for study, taking a first step toward analyzing the conditions and developing a therapies.

In addition to its stem cell work, Jaenisch’s lab is investigating epigenetic mechanisms for certain types of cancer and for brain development, studying how conditions such as Rett Syndrome occur.

Selected publications

Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R, Lengner CJ, Dausman JA, Jaenisch R. (2008) Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell. 133(2):250-64.

Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R. (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A. 105(15):5856-61.

Hanna J, Wernig M, Markoulaki S, Sun CW, Meissner A, Cassady JP, Beard C, Brambrink T, Wu LC, Townes TM, Jaenisch R. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. (2007) Science. 318(5858):1920-3.

Wernig M, Meissner A, Foreman R, Brambrink T, Ku M, Hochedlinger K, Bernstein BE, Jaenisch R. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. (2007) Nature. 19;448(7151):318-24.

Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, Lee TI, Levine SS, Wernig M, Tajonar A, Ray MK, Bell GW, Otte AP, Vidal M, Gifford DK, Young RA, Jaenisch R. Polycomb complexes repress developmental regulators in murine embryonic stem cells. (2006) Nature. 18;441(7091):349-53.

Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA. (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell. 122(6):947-56.

Eggan K, Baldwin K, Tackett M, Osborne J, Gogos J, Chess A, Axel R, Jaenisch R. (2004). Mice cloned from olfactory sensory neurons. Nature. 428(6978):44-9.

Hochedlinger, K. & Jaenisch, R. (2002). Generation of monoclonal mice by nuclear transfer from mature B and T donor cells. Nature 415, 1035-1038.

[research summary]

[publications (pubmed database)]