Recommended Readings: Lydia Finley, Ph.D., March 30

Special Lecture
Wednesday, March 30
4:00 p.m., Carson Family Auditorium (CRC)

Lydia Finley, Ph.D.
Jack Sorrell Fellow,
Damon Runyon Cancer Research Foundation,
Cancer Biology and Genetics Program,
Memorial Sloan Kettering Cancer Center

Metabolic Regulation of Cell Fate Decisions

Recommended Readings

Carey, B. W., Finley, L. W., Cross, J. R., Allis, C. D., & Thompson, C. B. (2015). Intracellular [agr]-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature, 518(7539), 413-416.  doi: 10.1038/nature13981.

Intlekofer, A. M., Dematteo, R. G., Venneti, S., Finley, L. W., Lu, C., Judkins, A. R., … & Thompson, C. B. (2015). Hypoxia induces production of L-2-hydroxyglutarate, Cell Metabolism, 22(2), 304-311. doi: 10.1016/j.cmet.2015.06.023.

Jeong, S. M., Xiao, C., Finley, L. W., Lahusen, T., Souza, A. L., Pierce, K., … & Xu, X. (2013). SIRT4 has tumor-suppressive activity and regulates the cellular metabolic response to DNA damage by inhibiting mitochondrial glutamine metabolism. Cancer Cell, 23(4), 450-463. doi: 10.1016/j.ccr.2013.02.024.

Laurent, G., de Boer, V. C., Finley, L. W., Sweeney, M., Lu, H., Schug, T. T., … & Haigis, M. C. (2013). SIRT4 represses peroxisome proliferator-activated receptor α activity to suppress hepatic fat oxidation. Molecular and Cellular Biology, 33(22), 4552-4561. doi: 10.1128/MCB.00087-13.

Recommended Readings: John Stamatoyannopoulos, M.D., May 11th

Special Lecture
Monday, May 11, 2015
4:00 p.m., Carson Family Auditorium (CRC)

John Stamatoyannopoulos, M.D.
Associate Professor of Genome Sciences and Medicine,
University Washington School of Medicine

New Insights into Human Genome Function

Recommended Readings

Empirical Articles

ENCODE Project Consortium. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489(7414), 57-74. doi:10.1038/nature11247

Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., … & Kulkarni, A. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518(7539), 317-330. doi:10.1038/nature14248

Mayer, A., di Iulio, J., Maleri, S., Eser, U., Vierstra, J., Reynolds, A., … & Churchman, L. S. (2015). Native elongating transcript sequencing reveals human transcriptional activity at nucleotide resolution. Cell, 161(3), 541-554. doi:10.1016/j.cell.2015.03.010

Yue, F., Cheng, Y., Breschi, A., Vierstra, J., Wu, W., Ryba, T., … & Morrissey, C. S. (2014). A comparative encyclopedia of DNA elements in the mouse genome. Nature, 515(7527), 355-364. doi:10.1038/nature13992

Review Paper

Kellis, M., Wold, B., Snyder, M. P., Bernstein, B. E., Kundaje, A., Marinov, G. K., … & Hardison, R. C. (2014). Defining functional DNA elements in the human genome. Proceedings of the National Academy of Sciences, 111(17), 6131-6138. doi:10.1073/pnas.1318948111

Recommended Readings: Talking Science, Monday, December 30

Talking Science
Caspary Auditorium
Monday, December 30, 2013
10:30 a.m.-2:30 p.m.

C. David Allis, Ph.D.
Joy and Jack Fishman Professor
Laboratory of Chromatin Biology and Epigenetics
The Rockefeller University

Epigenetics: Inheriting More Than Genes

Recommended Reading:

Epigenetics Basics

Simmons, D. (2008) Epigenetic influence and diseaseNature Education 1(1):6

In-Depth Reading

Feinberg, A. P. (2008). Epigenetics at the epicenter of modern medicine. JAMA : The Journal of the American Medical Association, 299(11), 1345–1350. doi:10.1001/jama.299.11.1345

Goldberg, A. D., Allis, C. D., & Bernstein, E. (2007). Epigenetics: a landscape takes shape. Cell, 128(4), 635–638. doi:10.1016/j.cell.2007.02.006

Recommended Readings: Pardis Sabeti M.D., Ph.D. Friday, Nov 8

Friday, November 8, 2013
3:45 p.m., Caspary Auditorium

Pardis Sabeti M.D., Ph.D.
Senior Associate Member, Broad Institute of MIT and Harvard;
Associate Professor, Center for Systems Biology, Harvard University Department of Organismic and Evolutionary Biology, and Department of Immunology and Infectious Disease at Harvard School of Public Health

Evolutionary Forces in Humans and Pathogens

Recommended Readings:

Empirical Articles

The 100 Genomes Project Consortium. (2010). A map of human genome variation from population-scale sequencing. Nature, 467(7319), 1061–1073. doi:10.1038/nature09534

The International MapMap Consortium. (2005). A haplotype map of the human genome. Nature, 437(7063), 1299–1320. doi:10.1038/nature04226

Grossman, S. R., Andersen, K. G., Shlyakhter, I., Tabrizi, S., Winnicki, S., Yen, A., … Sabeti, P. C. (2013). Identifying recent adaptations in large-scale genomic data. Cell, 152(4), 703–713. doi:10.1016/j.cell.2013.01.035

Sabeti, P. C., Reich, D. E., Higgins, J. M., Levine, H. Z., Richter, D. J., Schaffner, S. F., … & Lander, E. S. (2002). Detecting recent positive selection in the human genome from haplotype structureNature419(6909), 832-837. doi:10.1038/nature01140

Sabeti, P. C., Varilly, P., Fry, B., Lohmueller, J., Hostetter, E., Cotsapas, C., … Gaudet, R. (2007). Genome-wide detection and characterization of positive selection in human populations. Nature, 449(7164), 913–8. doi:10.1038/nature06250

Review Papers

Biswas, S., Akey, J. M. (2006) Genomic insights into positive selection. Trends in Genetics, 22(8), 437-445. doi:10.1016/j.tig.2006.06.005

Kreitman, M. (2000). Methods to detect selection in populations with applications to the human. Annual Review of Genomics and Human Genetics, 1, 539-559. doi: 10.1146/annurev.genom.1.1.539

Nielsen, R., Hellmann, I., Hubisz, M., Bustamante, C., & Clark, A. G. (2007). Recent and ongoing selection in the human genome. Nature Reviews Genetics,8(11), 857-868. doi:10.1038/nrg2187

Sabeti, P. C., Schaffner, S. F., Fry, B., Lohmueller, J., Varilly, P., Shamovsky, O., … & Lander, E. S. (2006). Positive natural selection in the human lineage .Science, 312(5780), 1614-1620. doi:10.1126/science.1124309

Vitti, J. J., Cho, M. K., Tichkoff, S. A., Sabeti, P. C. (2012). Human evolutionary genomics: ethical and interpretive issues. Trends in Genetics, 28(3), 137-145. doi:10.1016/j.tig.2011.12.001

New Study Sheds Light On Critical Nature Of DNA Methylation On Brain Development

For the first time, scientists have tracked the activity, across the lifespan, of an environmentally responsive regulatory mechanism that turns genes on and off in the brain’s executive hub. Among key findings of the study by National Institutes of Health scientists: genes implicated in schizophrenia and autism turn out to be members of a select club of genes in which regulatory activity peaks during an environmentally-sensitive critical period in development. The mechanism, called DNA methylation, abruptly switches from off to on within the human brain’s prefrontal cortex during this pivotal transition from fetal to postnatal life. As methylation increases, gene expression slows down after birth.

Read about it in NIH News.

Recommended Readings: Jeannie T. Lee, M.D., Ph.D.

Friday Lecture Series

Richard M. Furlaud Distinguished Lecture

X-Chromosome Inactivation as a Model for Epigenomic Regulation by Long

Noncoding RNAs

Jeannie T. Lee, M.D., Ph.D., professor of genetics and pathology,

Harvard Medical School, investigator,

Howard Hughes Medical Institute

January 27, 2012

3:45 p.m.-5:00 p.m. (Refreshments, 3:15 p.m., Abby Lounge)

Caspary Auditorium

Recommended Readings:

Lengner, C. J., A. A. Gimelbrant, J. A. Erwin, A. W. Cheng, M. G. Guenther, G. G. Welstead, R. Alagappan, et al. 2010. Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141, (5): 872-883

Namekawa, S. H., B. Payer, K. D. Huynh, R. Jaenisch, and J. T. Lee. 2010. Two-step imprinted X inactivation: Repeat versus genic silencing in the mouse. Molecular and cellular biology 30, (13): 3187-3205

Sarma, K., P. Levasseur, A. Aristarkhov, and J. T. Lee. 2010. Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of xist RNA localization to the X chromosome. Proceedings of the National Academy of Sciences of the United States of America 107, (51): 22196-22201

Tian, D., S. Sun, and J. T. Lee. 2010. The long noncoding RNA, jpx, is a molecular switch for X chromosome inactivation. Cell 143, (3): 390-403

Zhou, D., C. Conrad, F. Xia, J. -S Park, B. Payer, Y. Yin, G. Y. Lauwers, et al. 2009. Mst1 and Mst2 maintain hepatocyte quiescence and Suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell 16, (5): 425-438

The Fates of Embryonic Cells Indicated by Epigenetic Markers

Discovering the step-by-step details of the path embryonic cells take to develop into their final tissue type is the clinical goal of many stem cell biologists. To that end, Kenneth S. Zaret, PhD, professor of Cell and Developmental Biology at the Perelman School of Medicine at the University of Pennsylvania, and associate director of the Penn Institute for Regenerative Medicine, and Cheng-Ran Xu, PhD, a postdoctoral researcher in the Zaret laboratory, looked at immature cells called progenitors and found a way to potentially predict their fate. They base this on how histones are marked by other proteins.  Read about this research in the May 20, 2011 issue of SCIENCE.

New Evidence for Influence of Epigenetics

 Scientists at the Centre for Addiction and Mental Health (CAMH) have found evidence that a secondary molecular mechanism called epigenetics may also account for some inherited traits and diseases.  Epigenetic factors may help explain currently unclear issues in human disease, such as the presence of a disease in only one monozygotic twin, the different susceptibility of males (e.g. to autism) and females (e.g. to lupus), significant fluctuations in the course of a disease (e.g. bipolar disorder, inflammatory bowel disease, multiple sclerosis), among numerous others.   These factors represent a new way to look for the molecular cause of disease, and eventually may lead to improved diagnostics and treatment.   See the research reported in Nature Genetics advance online publication January 2009.