Recommended Readings: Peter Campbell, Ph.D. March 31, 2017

Friday Lectures

Friday, March 31, 2017   3:45 p.m.

Caspary Auditorium

Peter Campbell, Ph.D.

Head of Cancer Genetics and Genomics,

The Wellcome Trust Sanger Institute

Interrogating the Architecture of Cancer Genomes

Recommended Readings:

The Past, Present and Future of Genome Sequencing

Forbes, Simon A.; Beare, David; Gunasekaran, Prasad; et al. (2015). COSMIC: exploring the world’s knowledge of somatic mutations in human cancer. NUCLEIC ACIDS RESEARCH. 43(D1): D805-D811

Martincorena, Inigo; Campbell, Peter J. (2015). Somatic mutation in cancer and normal cellsSCIENCE.  349(6255): 1483-1489

Alioto, Tyler S.; Buchhalter, Ivo; Derdak, Sophia; et al. (2015). A comprehensive assessment of somatic mutation detection in cancer using whole-genome sequencingNATURE COMMUNICATIONS. 6(10001)

Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.; et al. (2013). Signatures of mutational processes in human cancer. NATURE. 500(7463): 415-+

Yates, Lucy R.; Campbell, Peter J. (2012). Evolution of the cancer genome. NATURE REVIEWS GENETICS. 13(11): 795-806  

 

 

Recommended Readings: Julie Segre, Ph.D., February 12

Friday Lecture Series
Friday, February 12, 2016
3:45 p.m., Caspary Auditorium

Julie Segre, Ph.D.,
Senior Investigator, Microbial Genomics Section,
Chief, Translational and Functional Genomics Branch,
National Human Genome Research Institute,
National Institutes of Health

Human Skin Microbiome in Health and Disease

Recommended Reading

Empirical Papers

Conlan, S., Thomas, P. J., Deming, C., Park, M., Lau, A. F., Dekker, J. P., … & Segre, J. A. (2014). Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae. Science Translational Medicine, 6(254), 254ra126-254ra126. doi: 10.1126/scitranslmed.3009845.

Naik, S., Bouladoux, N., Linehan, J. L., Han, S. J., Harrison, O. J., Wilhelm, C., … & Belkaid, Y. (2015). Commensal-dendritic-cell interaction specifies a unique protective skin immune signature. Nature, 520(7545), 104-108. doi: 10.1038/nature14052.

Oh, J., Byrd, A. L., Deming, C., Conlan, S., Kong, H. H., Segre, J. A., & NISC Comparative Sequencing Program. (2014). Biogeography and individuality shape function in the human skin metagenome. Nature, 514(7520), 59-64. doi: 10.1038/nature13786.

Review Article

Belkaid, Y., & Segre, J. A. (2014). Dialogue between skin microbiota and immunity. Science, 346(6212), 954-959. doi: 10.1126/science.1260144.

Recommended Readings: Elena Gallo MacFarlane, Ph.D., February 8

Special Seminar
Wednesday, February 8, 2016
4:00 p.m., Carson Family Auditorium (CRC)

Elena Gallo MacFarlane, Ph.D.
Postdoctoral and Research Fellow,
Institute of Genetic Medicine,
Johns Hopkins University School of Medicine

The Vessel Wall as a Paracrine Engine in TGF-Beta-Driven Vasculopathies

Recommended Reading:

Chetaille, P., Preuss, C., Burkhard, S., Côté, J. M., Houde, C., Castilloux, J., … & Thibeault, M. (2014). Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm. Nature Genetics, 46(11), 1245-1249. doi: 10.1038/ng.3113.

Gallo, E. M., Loch, D. C., Habashi, J. P., Calderon, J. F., Chen, Y., Bedja, D., … & Judge, D. P. (2014). Angiotensin II–dependent TGF-β signaling contributes to Loeys-Dietz syndrome vascular pathogenesis. The Journal of Clinical Investigation, 124(1), 448-460. doi: 10.1172/JCI69666.

Gerber, E. E., Gallo, E. M., Fontana, S. C., Davis, E. C., Wigley, F. M., Huso, D. L., & Dietz, H. C. (2013). Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of scleroderma. Nature, 503(7474), 126-130. doi: 10.1038/nature12614.
Chicago

Lindsay, M. E., Schepers, D., Bolar, N. A., Doyle, J. J., Gallo, E., Fert-Bober, J., … & Bjeda, D. (2012). Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm. Nature Genetics, 44(8), 922-927. doi: 10.1038/ng.2349

Recommended Readings: Michael Lenardo, M.D., October 23rd

Friday Lecture Series
Friday, October 23, 2015
3:45 p.m., Caspary Auditorium

Michael Lenardo, M.D.
Chief, Molecular Development Section,
Laboratory of Immunology,
Director, NIAID Clinical Genomics Program,
National Institute of Allergy and Infectious Diseases,
National Institutes of Health

Genomic Approaches to Solving Primary Immune Disorders

Recommended Readings

Empirical Articles

Kuehn, H. S., Ouyang, W., Lo, B., Deenick, E. K., Niemela, J. E., Avery, D. T., … & Uzel, G. (2014). Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science, 345(6204), 1623-1627. doi:10.1126/science.1255904.

Lo, B., Zhang, K., Lu, W., Zheng, L., Zhang, Q., Kanellopoulou, C., … & Jordan, M. B. (2015). Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science, 349(6246), 436-440. doi:10.1126/science.aaa1663.

Lucas, C. L., Zhang, Y., Venida, A., Wang, Y., Hughes, J., McElwee, J., … & Lenardo, M. J. (2014). Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. The Journal of Experimental Medicine, 211(13), 2537-2547. doi:10.1084/jem.20141759.

Review Papers

Grönholm, J., & Lenardo, M. J. (2015). Novel diagnostic and therapeutic approaches for autoimmune diabetes- A prime time to treat insulitis as a disease. Clinical Immunology, 156(2), 109-118. doi:10.1016/j.clim.2014.11.007.

Zhang, Y., Su, H. C., & Lenardo, M. J. (2015). Genomics is rapidly advancing precision medicine for immunological disorders. Nature Immunology, 16(10), 1001-1004. doi:10.1038/ni.3275

Recommended Readings: Carl H. June, M.D., May 22nd

Friday Lecture Series
Friday, May 22, 2015
3:45 p.m., Caspary Auditorium

Carl H. June, M.D.
Director, Translational Research Program,
Abramson Family Cancer Research Institute
Richard W. Vague Professor in Immunotherapy,
Perelman School of Medicine,
University of Pennsylvania

Adoptive Cell Therapy with Engineered T Cells

Recommended Readings

Empirical Articles

Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., … & June, C. H. (2013). Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. New England Journal of Medicine, 368(16), 1509-1518.  doi:10.1056/NEJMoa1215134

Kalos, M., Levine, B. L., Porter, D. L., Katz, S., Grupp, S. A., Bagg, A., & June, C. H. (2011). T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Science Translational Medicine, 3(95), 95ra73-95ra73. doi:10.1126/scitranslmed.3002842

Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011). Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia. New England Journal of Medicine, 365(8), 725-733. doi:10.1056/NEJMoa1103849

Review Papers

June, C. H., Maus, M. V., Plesa, G., Johnson, L. A., Zhao, Y., Levine, B. L., … & Porter, D. L. (2014). Engineered T cells for cancer therapy. Cancer Immunology, Immunotherapy, 63(9), 969-975. doi:10.1007/s00262-014-1568-1

Maus, M. V., Fraietta, J. A., Levine, B. L., Kalos, M., Zhao, Y., & June, C. H. (2014). Adoptive immunotherapy for cancer or viruses. Annual Review of Immunology, 32, 189-225. doi:10.1146/annurev-immunol-032713-120136

NIH News: IOM Report on the Complexities of Translating “Omics” Into Treatment

WASHINGTON — Genomics, proteomics, and other branches of molecular bioscience offer the prospect of greater precision in medical care, but some clinical tests based on “omics” research have proved invalid and highlighted the challenges of dealing with complex data.  To enhance the translation of omics-based discoveries to clinical use, a new report by the Institute of Medicine recommends a detailed process to evaluate whether the data and computational steps underlying such tests are sound and the tests are ready to be used in clinical trials.  The proposed process defines responsibilities and best practices for the investigators, research institutions, funders, regulators, and journals involved in development and dissemination of clinical omics-based technologies.

Recommended Readings: Barry S. Coller M.D. Monday Sept 26 2011

Monday Lectures

Combing Structure-Based Design and Mass Screening to Probe

 Ligand Binding to Integrin Receptors

Barry S. Coller  M.D.

Vice President for Medical Affairs and Physician-in-Chief

Laboratory of Blood and Vascular Biology

September 26, 2011,  Caspary Auditorium,  4 p.m.

Recommended Readings

Litvinov RI; Barsegov V; Schissler AJ; Fisher AR; Bennett JS; Weisel JW; Shuman H.  2011.  Dissociation of bimolecular αIIβ3-fibrinogen complex under a constant tensile force.   Biophysical Journal.  100(1):165-73.

Lord MS; Cheng B; McCarthy SJ; et al.  2011.  The modulation of platelet adhesion and activation by chitosan through plasma and extracellular matrix proteins.  Biomaterials. 32(28):6655-6662  (Request from Markus Library)

Blue R; Li JH; Steinberg J; et al.  2010.  Effects of limiting extension at the alpha IIb Genu on ligand binding to integrin alpha IIb beta 2.  Journal of Biological Chemistry.  285(23):17604-17613.

Sheldrake HM; Patterson LH.  2009.  Function and antagonism of beta(3) integrins in the development of cancer therapyCurrent Cancer Drug Targets. 9(4):519-540.  (Request from Markus Library)

Basani RB; Zhu H: Thornton MA: et al.  2009.  Species differences in small molecule binding to alpha IIb beta 3 are the result of sequence difference in 2 loops of the alpha IIb beta propeller.   Blood.  113(4):902-910.

Blue R; Kowalska MA; Hirsch J; et al.  2009.  Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alpha IIb beta 3 antagonist. Blood  114(1):195-201

Blue R; Murcia M; Karan C; et al.  2008.  Application of high-throughput screening to identify a novel alpha IIb-specific small-molecule inhibitor of alpha IIb 3-mediated platelet interaction with fibrinogen.  Blood.  111(3):1248-1256.

Hynes, RO.  2002.  Integrins: bidirectional, allosteric signaling machinesCell. 110(6):673-687.

Rockefeller One of Ten Sites Receiving Renewed Translational Medicine Grants

NEW YORK (GenomeWeb News) – Ten research institutes have received a total of $498 million from the National Center for Research Resources to fund the second five-year phase of their Clinical and Translational Science Institutes.

The largest awards in this second round of Clinical and Translational Science Awards funding include a $112 million grant to the University of California, San Francisco; $67.3 million to the University of Pittsburgh; $62.8 million to Mayo Clinic; and $54.8 million to the University of Pennsylvania.

Other research centers receiving the latest round of CTSA funding include Yale University ($45.4 million); Oregon Health & Sciences University ($39.8 million); Columbia University Medical Center ($38.9 million); Rockefeller University ($36.1 million); University of Rochester ($20.7 million); and UC Davis ($20 million).

“These institutes were the pioneers in this program and are to be commended for the work they have done in bridging the traditional divides between laboratory research and medical practice,” Barbara Alving, director of the National Center for Research Resources, said in a statement from UCSF.

“They were tasked with transforming the way their institutions coordinate research to make it more proactive and effective in producing real-world results, and in the process, they have served as innovative models nationwide,” Alving said.

According to UCSF, the National Institutes of Health plans to release a report on the CTSA program in August that will highlight the research that has sprung from this program.

UCSF said that the CTSA grants have supported the creation of a framework to enable researchers to “move beyond the traditional silos of science to collaborate on promising research and find the training and resources to move those projects ahead.”

The university said that at UCSF the funding has enabled the creation of “an extensive network of training and support for researchers to help bridge the gaps between laboratory science, clinical care, and improvements in health.”

President’s NIH Proposed Budget Highlights Genomics, Translational Efforts

In The National Institutes of Health’s $31.83 billion budget proposal for 2012, NIH Director Francis Collins said the institute plans to focus much of its efforts on leveraging new genomics technologies in disease and health research and translational science, and in pursuing goals in personalized medicine.

Collins said the funding, an increase of 2.4 percent over the most recent budget to pass (2010), “will enhance NIH’s ability to support research that prolongs life, reduces disability, and strengthens the economy.”

The White House yesterday unveiled its budget proposal for Fiscal Year 2012 — a plan aimed at cutting spending in general by trimming in targeted areas, but which includes moderate increases for funding and supporting research and development.

Research-oriented groups appreciated that the President and his budget team spared science funding while making cuts to other programs.

NIH Board Approves New Translational Institute

National Institutes of Health Director Francis Collins says the agency has taken a “bold step”  deciding to create a new NIH center that will focus on advancing translational medicine and therapeutics (TMAT), and which will have major implications for the National Center for Research Resources.

The new center’s mission will be to support, foster, and catalyze TMAT research and serving as a resource for the business sector.   It will do so by taking over several of NCRR’s current programs, the TMAT Working Group of NIH’s Scientific Management Review Board (SMRB) agreed yesterday.  The TMAT center arose out of the scientific need for new approaches and avenues for getting medicine from the lab to the clinic more swiftly and cost-effectively. Collins aims to have the center funded by the 2012 fiscal year.