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Biochemistry & Molecular Biology - George Adrouny Lecture

18th Annual George Adrouny Lecture and the History of the Adrouny Memorial Lectureship

Fred Alt

18th Annual George Adrouny Lecture and the History of the Adrouny Memorial Lectureship

The Department of Biochemistry and Molecular Biology was proud to present the 18th Annual George Adrouny Memorial Lectureship on Friday, May 10th, 2019, at 9:30am in the 1st Floor Auditorium of the Tulane University School of Medicine, 1430 Tulane Avenue. 

The 2019 featured speaker was Frederick W. Alt, PhD.  Frederick Alt received his Ph.D. in Biology from Stanford University in 1977 where he worked with Robert Schimke and discovered gene amplification and genomic instability in mammalian cancer cells. Alt moved to MIT for postdoctoral work with David Baltimore, where he helped elucidate basic principles of recombination in the immune system. His work with David Baltimore included the discovery that production of membrane versus secreted immunoglobulin is achieved via differential RNA processing and the discovery that allelic exclusion of Immunoglobulin (Ig) gene rearrangements is controlled by feedback from protein products. With Baltimore, Alt also elucidated major aspects of the V(D)J recombination mechanism, including involvement of site-specific DNA double strand breaks (DSBs) that are end joined, as well as the discovery of ”N” regions added by terminal deoxynucleotydl transferase (TdT) that provide a major source of antigen receptor diversity.

Dr. Alt moved to Columbia University in 1982 as Assistant Professor of Biochemistry. He became Professor of Biochemistry and Molecular Biophysics in 1985 and HHMI Investigator in 1987. At Columbia, his lab established the role of Ig chains in regulating sequential stages of B cell development and discovered that all antigen receptor genes are assembled by a common V(D)J recombinase. They then elucidated a role for non-coding gene transcription in mediating "chromatin accessibility" as means to target the lineage, stage, and allele specific activity of the V(D)J recombinase. His group extended that work to show that, in B cells, IgH class switch recombination (CSR) to particular IgH classes is directed by activation of non-coding transcription units that contain the CSR target sequences. At Columbia, the Alt lab also co-discovered the N-myc cellular oncogene, based on its amplification in human neuroblastomas and he went on to characterize the Myc cellular oncogene family.

In 1991, Dr. Alt moved to Boston Children' Hospital (BCH) and Harvard Medical School as a Professor of Genetics and HHMI Investigator. He also became a Senior Investigator at the Immune Disease Institute (IDI). He was appointed Charles A. Janeway Professor of Pediatrics in 1993, Scientific Director of IDI in 2005, and Director of the Program in Cellular and Molecular Medicine (PCMM) at BCH in 2008. He also became President of IDI in 2010 and continues to serve as director since the merger of IDI with BCH, where it remains the PCMM. At BCH and IDI, Dr. Alt's group confirmed the proposal of Alt and Baltimore that N regions are added by terminal dexoynucleotidyl transferase, demonstrating that TdT is a V(D)J recombinase component. They also discovered that the joining activity of the V(D)J recombinase is carried out by a novel multi-component general cellular non-homologous DNA end joining now known as the major C-NHEJ DSB repair pathway. Subsequently, the Alt lab was involved in the discovery of a number of the first characterized NHEJ component factors and then went on to discover the key role of NHEJ proteins in maintenance of genomic stability.

The Alt lab continues to elucidate many new aspects of the mechanism and control of V(D)J recombination including discovering that this reaction is regulating by a process that allows the initiating RAG endonuclease V(D)J recombination factors to explore directionally within chromosomal loop domains for target substrates. His lab also continues to discover new aspects of the mechanism and regulation IgH CSR and the related process of Ig variable region exon somatic hypermutation. The lab's recent work, based on their development of high through-put methods to study DSBs and chromosomal translocations, have provided major new insights into the mechanisms that contribute to chromosomal rearrangements within the 3D genome of developing lymphocytes and cancer cells or their progenitors. The lab also has used their new approaches to identify a set of genes that recurrently break in neuronal stem and progenitor cells and, thereby, which may contribute to brain diversification and neuropsychiatric diseases and cancer. Most recently, the lab has built on their more basic molecular immunology discoveries on antibody gene assembly to generate innovative new mouse models for testing immunization strategies for eliciting HIV-1 broadly neutralizing antibodies.

Frederick Alt has been elected to the National Academy of Sciences, the Institute of Medicine (National Academy of Medicine), the American Academy of Arts and Sciences, and the European Molecular Biology Organization. His cancer biology awards include the American Association of Cancer Research Clowes Award, the Pasarow Foundation Prize for Extraordinary Achievement in Cancer Research, the National Cancer Institute Alfred K. Knudson Award for "Pioneering Contributions that Revolutionized the Field of Cancer Genetics", the Leukemia and Lymphoma Society de Villiers Award, The Katharine Berkan Judd Award from Memorial Sloan Kettering Cancer Center, the Albert Szent-Gyorgyi Prize for Progress in Cancer Research from the National Foundation for Cancer Research, and the American-Italian Cancer Foundation Prize for Excellence in Medicine. His immunology awards include the American Association of Immunologists (AAI) Huang Meritorious Career Award, the Cancer Research Institute (CRI) Coley Award, and the Novartis Prize for Basic Immunology. More generally, he has also received the Arthur Kornberg & Paul Berg Lifetime Achievement Award in Biomedical Science and the Lewis S. Rosensteil Prize for Distinguished work in Biomedical Sciences. Dr. Alt serves on numerous editorial boards and is Editor in Chief of Advances in Immunology. He also serves on many national and international advisory boards and is currently Chair of the Scientific Advisory Committee of the Cold Spring Harbor Laboratory. Dr. Alt has mentored over 100 students and research fellows, many of whom have become leaders in immunology, genetics, or cancer biology and he received the American Association of Immunologists Excellence in Mentoring Award and the Willam A. Silen Award for Lifetime Achievement in Mentoring from Harvard Medical School. The Cancer Research Institute of New York annually presents the Frederick W. Alt Award for New Discoveries in Immunology.

His research interests center on understanding the mechanisms and regulation of gene expression in mammalian cells. His work has been supported by many grants, including an NIH MERIT Award. He has authored or coauthored over 330 research articles and reviews on these topics, and is an ISI Highly Cited Researcher. Manley is or has been an Editor of three journals and has served on numerous editorial boards and review panels. He is a Fellow of the American Academy of Microbiology, the American Academy of Arts and Sciences and the American Association for the Advancement of Science, and a member of the National Academy of Sciences.

Dr. Manley's laboratory studies gene expression in mammalian cells.  Manley and his colleagues identified and characterized the key factors responsible for polyadenylation of mRNA precursors, and elucidated how this remarkably complex machinery functions in gene regulation, for example during cell growth and differentiation. He has also studied the mechanism and regulation of the process by which introns are removed from mRNA precursors, mRNA splicing. Manley and his coworkers co-discovered the first alternative splicing factor (SR protein), characterized how this and other splicing regulatory proteins function and are themselves regulated, showed how alternative splicing can become deregulated in disease, and with respect to mechanism demonstrated that two spliceosomal small nuclear RNAs by themselves have catalytic activity. Finally, he elucidated unexpected links between these mRNA processing reactions and transcription, DNA damage signaling and maintenance of genomic stability. His work has thus provided considerable insight into the complex mechanisms that are essential for the regulated production of mRNAs in mammalian cells.

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The History of the George Adrouny Memorial Lecture

As a memorial to their late father, the distinguished former Professor of Biochemistry, George A. Adrouny, a memorial lectureship was established in 2000 by his children and family to honor his memory. The Department of Biochemistry, Tulane University Health Sciences Center, School of Medicine, is proud to host this annual event.

George AdrounyGeorge A. Adrouny was born of Armenian parents in Turkey on April 2, 1912. He received his B.A. in chemistry in 1934, and a degree in pharmaceutical chemistry in 1940, both from the American University of Beirut. While working as a freelance pharmacist, he also taught chemistry and biology at Aleppo College in Aleppo, Syria. In 1951, a Smith-Mundt Fellowship permitted him to begin graduate studies at Emery University where he earned a Ph.D. in Biochemistry in 1954. After two years as a Research Associate in Biochemistry at Emory, he was recruited to the Tulane University School of Medicine, Department of Biochemistry, where he ultimately rose to the rank of full professor. 

Dr. Adrouny’s research interests were diverse. His identification and characterization of the fire ant venom was published in 1959 in Science magazine. He also published papers in the areas of cardiac glycogen metabolism, intestinal dextran-hydrolyzing enzymes, biochemical effects of growth hormone and the phylogenic and evolutionary importance of hickory nut and pecan oils. 

He headed the Foreign Fellows Program, specifically created for foreign graduate students studying at Tulane. He also was placed in charge of the Medical Biochemistry course, a post that he enjoyed until his retirement in 1981. In recognition of his devotion to the organization and teaching of this course, the Owl Club gave him a certificate of recognition in 1981. He was named Professor Emeritus following his retirement from the Medical School. 

Dr. Adrouny was a member of the Society of Sigma Xi, the New York Academy of Sciences, the American Chemical Society and he was a Fellow of the American Association for the Advancement of Sciences. He was listed in the Who’s Who of American Education in 1967-68. 

In 1987, a few years after the death of Alice K. Adrouny, his wife of 38 years, Dr. Adrouny moved to Maryland to be near family where he lived until his death on November 24, 1999.

Previous Keynote Speakers

April 19, 2018
James Manley, PhD
Julian Clarence Levi Professor of Life Sciences
Columbia University
New York, New York
Disregulation of mRNA splicing in myelodysplastic syndromes and cancer

April 10, 2017
Judith Campisi, PhD
Professor of Biogerontology
Buck Institute for Research on Aging
Senior Scientist, Lawrence Berkeley National Laboratory
Novato, California
Cancer and Aging:  Rival Demons?

April 11, 2016
Hongtao Yu, PhD
Michael L. Rosenberg Scholar in Medical Research
Department of Pharmacology
Howard Hughes Medical Institute
University of Texas Southwestern Medical Center
Houston, Texas
Mitotic regulators in chromosome segregation and beyond

November 1, 2015 (in conjunction with the 8th International MDM2 Workshop)
Carol Prives, PhD
DaCosta Professor of Biological Sciences
Department of Biological Sciences
Columbia University, New York, New York
p53-Dependent and Independent Roles of Mdm2 in Cancer Cells and Human Disease

April 14, 2014
Wei Gu, PhD
Abraham and Mildred Goldstein Professor
Department of Pathology & Cell Biology
Institute for Genetics
Herbert Irving Cancer Research Center
Columbia University
New York, New York
Do We Really Know How p53 Suppresses Tumorigenesis?

April 12, 2013
Arnold J. Levine, PhD
Institute for Advanced Studies, School of Natural Sciences, Princeton, New Jersey
The Evolution of the p53 Family of Genes and their Role in Cancer

May 21, 2012
Robert G. Roeder, PhD
Rockefeller University, New York, New York
Transcriptional Regulatory Mechanisms in Animal Cells

April 15, 2011
Ellen Sidransky, MD
National Institutes of Health, Bethesda, Maryland
Gaucher Disease and Parkinsonism:  Insights From a Rare Disorder

April 9, 2010
Thomas Seyfried, PhD
Boston College, Boston, Massachusetts
Ganglioside Storage Disease:  On the Road to Management

April 17, 2009
Stephen G. Sligar, PhD
University of Illinois, Urbana, Illinois
Elucidating the Structure and Function of Membrane Proteins through Nanotechnology

April 7, 2008
Marlene Belfort, PhD
NYS Department of Health, Center for Medicine, Albany, New York
Genome Invaders:  Mobile Self-Splicing Introns in Bacteria

April 13, 2007
Gerald W. Hart, PhD
Johns Hopkins University School of Medicine, Bethesda, Maryland
Dynamic Cycling of O-GlcNAc:  Interplay with Phosphorylation and Roles in Diabetes, Signaling and Transcription

2005 and 2006 – Hurricane Katrina – no lectures

October 1, 2004
Diana S. Beattie, PhD
West Virginia University School of Medicine, Morgantown, West Virginia
The Unique Mitochondrion of the African Parasite, Trypanosoma brucei

September 8, 2003
Tim Townes, PhD
University of Alabama, Birmingham, Alabama
Human Globin Gene Regulation and Genetic Strategies for Correcting Thalassemias and Sickle Cell Disease

September 23, 2002
Dagmar Ringe, PhD
Brandeis University, Waltham, Massachusetts
From Sequence to Function: How Easy Is It?

September 10, 2001
Billy Hudson, PhD
University of Kansas Medical Center, Kansas City, Kansas
Basement Membrane Collagen: An Ancient Protein Essential for Tissue Development

November 6, 2000
Kenneth G. Mann, PhD
University of Vermont, Burlington, Vermont
Blood Coagulation at the Turn of the Century