Women's History Month: CSHL Women in Science

Dafna Bar-Sagi was a Senior Staff Investigator at Cold Spring Harbor Laboratory from 1984-1994. In 1986 Dr. Bar-Sagi and her postdoc advisor, Dr. James Feramisco observed that injection of oncogenic KRAS protein into fibroblasts caused morphological changes, including pronounced membrane ruffling and the accumulation of pinocytic vesicles. Recent investigations into the metabolism of cancers, especially cancers driven by mutant KRAS, have transformed macropinocytosis from a phenotypic curiosity to a key player in the nutrition of pancreatic cancer cells.

Dafna is currently a Professor in the Departments of Biochemistry & Molecular Pharmacology and Medicine, and Senior Vice President and Vice Dean for Science at New York University’s School of Medicine.

Jim Feramisco, Dafna Bar-Sagi, ca. 1986

Source: CSHL Archives. https://www.cancer.gov/research/key-initiatives/ras/ras-central/blog/2016/dafna-bar-sagi-interview

In 1924, Dorothy Bergner replaced John Belling as Albert Blakeslee's principal coworker. Prior to her time in CSH,   Dorothy Bergner was the first to describe the natural occurrence of sporophytic haploids in the weed species Datura stramonium in 1922. With Bergner, Albert Blakeslee discovered a thirteenth trisomic in Datura. As there are only 12 chromosome pairs, a different explanation was sought, and found.  She is the author of eight papers related to plant science and genetics.  In 1937 it was discovered that colchicine will paralyze mitotic cell division and give rise to cells in which the chromosome number has been doubled. Using this technique, Blakeslee and Bergner produced polyploids, and periclinal chimeras. She worked at the C.I.W. Department of Genetics until 1942.

Martha Chase graduated from the College of Wooster in Ohio  in 1950 when she was hired as a research assistant by Dr. Alfred D. Hershey, a biologist who was investigating how viruses replicate. Working at the Cold Spring Harbor Laboratory in 1952, the two devised one of the most iconic and elegant experiments in modern biochemistry to determine whether DNA or protein carried genetic information.

Ms. Chase left Cold Spring Harbor in 1953 to work at the Oak Ridge National Laboratory in Tennessee and later at the University of Rochester. She returned to Cold Spring Harbor each summer during the 1950's to participate in the meetings of the influential Phage Group of biologists. In 1959, she began work on her doctorate at the University of Southern California. After receiving it in 1964, she returned to Cleveland. She passed away in Cleveland in 2003.

Louise Chow and her husband, UAB Professor Thomas Broker, joined the Cold Spring Harbor Laboratory in 1975. Initially, her work focused on the genetic organization, RNA transcription and DNA replication of human adenoviruses, which cause common respiratory and gastrointestinal tract infections. In the course of this work, in 1977, she and her collaborators discovered the totally unexpected phenomenon of split genes and RNA splicing. This work became the foundation for the understanding the human and the other eukaryotic genomes, the origin of most of their encoded proteins and the cause of many different genetic diseases. Chow was made Senior Staff Investigator in 1977 and Senior Scientist in 1979.

She left Cold Spring Harbor and joined the University of Rochester in 1984, where her team concentrated on distinguishing the growing number of human papillomavirus genotypes as well as the spliced structures of their mRNAs. Louise is currently a professor of Biochemistry and Molecular Genetics at the University of Alabama at Birmingham and a foreign associate with the National Academy of Sciences.

Source: CSHL Archives. https://en.wikipedia.org/wiki/Louise_Chow http://www.uab.edu/news/latest/item/2386-uab-louise-chow-elected-to-national-academy-of-science

Holly  Cline received her Ph.D. from the University of California, Berkeley in 1985.  She was a Professor of Neuroscience at Cold Spring Harbor for 14 years, from 1994 to 2010, where she made major contributions to the understanding of brain development and function. She was also Director of Research at CSHL from 2002 to 2006. During her time at Cold Spring Harbor, Cline researched mechanisms of neuronal growth in the brain, how synapses generate, and the development of sensory projection in different regions of the brain.

She was awarded National Institutes of Health Director's Pioneer Award in 2005 to launch a large-scale project to understand the architecture, development, and plasticity of brain circuits. She was one of only 13 scientists to receive this annual award, which recognizes scientists who have far-ranging ideas that hold the potential to make truly extraordinary contributions to many fields of medical research.  Holly is currently Co-Chair of the Neuroscience Department at the Scripps Institute.

Source: CSHL Archives

Paula De Lucia came to Cold Spring Harbor in 1964 under the guidance of Dr. John Cairns. In 1969 Paula DeLucia and John Cairns discover that the 5 to 3 polymerase I activity of DNA polymerase I in E. coli is not required for DNA replication.   

Because of Paula DeLucia and John Cairns, the main player in DNA replication was determined to be DNA Polymerase III, not polymerase I. One of the main functions of DNA Polymerase I is to repair damaged DNA. This mutation hindered the enzymatic ability to complete this task, thus reinforcing the idea that repair was one of the enzymes main purposes.

She was active at Cold Spring Harbor until 1971.

Source:  Jan Witkowski. The Road to Discovery: A Short History of Cold Spring Harbor Laboratory, CSHL Press. 2016. Cold Spring Harbor Laboratory Annual Report, 1971.

Lilian Clark Gann received her Ph.D. from the University of St. Andrews, Scotland in 1988, for her studies on DNA-protein interactions in transcriptional control elements of DNA tumor viruses, and received her M.B.A. from the University of Westminster, London in 1996.

Lilian joined the Laboratory in March 1999 as Assistant Dean of the Watson School and was promoted to Associate Dean in January 2002. She became Dean of the Watson School of Biological Sciences on July 1, 2004. Lilian played a crucial role in the development of the School's innovative Ph.D. program, while also enhancing the educational and training environment of CSHL for students and postdoctoral fellows in general. Her unique background in science, education, and business made her an obvious choice to develop and oversee the programs of the Watson School.

Mary Jane Gething earned her Ph.D. in Biochemistry in 1974 in the Department of Biochemistry and Molecular Biology at the University of Melbourne. She came to the Laboratory in 1982 to work with her husband Joe Sambrook on the transport and secretion of the hemagglutinin protein, which is found on the influenza virus. While at CSHL, Gething also worked on a cloning project for tPA (tissue plasminogen activator), one of the earliest projects in biotechnology done at the Laboratory.

In 1985, Gething and Sambrook moved to Dallas to work at the University of Texas Southwestern Medical Center. They moved back to Australia in 1994. She was until recently the Head of the Department of Biochemistry and Molecular Biology at the University of Melbourne. Her current research involves protein folding in the cell and the role of molecular chaperone BiP.

Carol W. Greider received a Ph.D. in 1987 from the University of California at Berkeley. In 1984, working together with Dr. Elizabeth Blackburn, she discovered telomerase, an enzyme that maintains telomeres. In 1988 Dr. Greider came to Cold Spring Harbor Laboratory where, as an independent Cold Spring Harbor Fellow, she cloned and characterized the RNA component of telomerase.  She was appointed as an Assistant Investigator in 1990, Associate Investigator in 1992, and Investigator at Cold Spring Harbor Laboratory in 1994.  She expanded the focus of her telomere research to include the role of telomere length in cell senescence, cell death, and cancer.Carol Greider was award the 2009 Nobel Prize for Medicine or Physiology with Elizabeth Blackburn and Jack Szostak for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. In 1997 Dr. Greider moved her laboratory to the Johns Hopkins University School of Medicine, where she is the Daniel Nathans Professor and Director of the Department of Molecular Biology and Genetics.

Rashika Harshey has made seminal contributions to two important areas of microbiology. Her work on phage Mu has elucidated difficult-to-decipher DNA transposition mechanisms, both in vivo and in vitro.

She received her Ph.D. from the Indian Institute of Science in Bangalore, India. She came to Cold Spring Harbor laboratory as a postdoc from 1979-1981. She was later promoted to a Staff Investigator from 1981-1982.

Dr. Harshey was elected a fellow in the American Academy of Microbiology in 2007. Dr. Harshey is currently a Professor of Molecular Biosciences at the University of Texas at Austin.

Source: Cold Spring Harbor Laboratory Archives, Annual Report Cold Spring Harbor Laboratory 1982.

Nouria Hernandez performed her thesis research on mRNA splicing with Dr. Walter Keller at the University of Heidelberg in Germany, receiving her PhD in 1983.  She did her postdoctoral studies with Dr. Alan M. Weiner at Yale University in New Haven working on 3’ end formation of the U1 small nuclear RNA. She then joined Cold Spring Harbor Laboratory in 1986 as a Senior Staff Investigator studying human small nuclear RNA (snRNA) genes, which encode snRNAs that are involved in RNA procession reactions such as mRNA splicing and transcription. She became a Senior Staff Scientist & Cold Spring Harbor Laboratory Professor in 1993 and she joined the Howard Hughes Medical Institute as an Associate Investigator in 1994. She became a Principal Investigator for Howard Hughes Medical Institute in 1997 and a full Howard Hughes Medical Institute Investigator in 1999. In 2005, she joined the faculty of the UNIL as a Professor and as the Director of the Center for Integrative Genomics (CIG).

Jill Davidson Hershey was a research assistant for Dr. H.E. Warmke at the Carnegie Institution of Washington Department of Genetics from 1943-1945. She would later collaborate with her husband, future Nobelist Alfred Day Hershey whom she married in November 1945. Hershey followed Jill to Cold Spring Harbor where she then worked with Vernon Bryon and Palmer D. Skaar. Her scientific background includes work on bacteria mutation and genetic studies of Escherichia coli. She stopped working at Cold Spring Harbor in 1965.

Source: Jill Davidson Hershey/Carnegie Institution of Washington Administrative Files/Cold Spring Harbor Laboratory Archives, Carnegie Institution of Washington Year Books # 1943-1945.

Zlata Demerec (Hartman) came to Cold Spring Harbor in 1941 as her father Milislav Demerec took over reins of the Carnegie Institution of Washington Department of Genetics, as well as the Long Island Biological Laboratory Biological Laboratory. She took the course in Bacterial Genetics in 1953 with instructors Vernon Bryson, her father and Evelyn Witkin. Milislav Demerec began a project with her…..Parallel work on this was being done by Philip Hartman who was working as a  Research Fellow of the U.S. Public Health Service.  The first progress report on this work was published in the C.I.W. in 1953, but by the time the paper was published Milislav Demerec,  Zlata and  Phil Hartman who had married . This paper  was an early hint of the operon concept which would be developed in full by Jacob and Monod, who cited the 1956 paper in their classic paper >>>>>>>>>She resigned from the Biological Laboratory in 1956.

Zlata Demerec Hartman was a pioneer of bacterial genetics and education. She had made numerous discoveries about the operon, bacterial metabolism, and mutagenesis. She also worked closely with her father and husband, Phil Hartman on a classic study of the fine structure of the gene and the linkage relations of the genes in Salmonella typhimurium.  She resigned in 1956.

Source: Jan Witkowski, The Road to Discovery: A Short History of CSHL. CSH Press, 2016.

Birgit Zipser was a student in the 1975 Leech course. In 1978 she was the first appointment made to the newly organized Neurobiology area at CSH, her title was Senior Staff Investigator.

In the spring of 1979, she helped organize an Invertebrate Neurobiology Workshop in Jones, using Marie H. Robertson funds. In 1978 Zipser started collaborating with Ron McKay.  She became the founding, and sole, member of the Neuroscience division, studying electrophysiology of leech ganglia.  She left Cold Spring Harbor in December of 1984. Since 1984 Dr. Zipser has studied the human brain, particularly enzymes related to Alzheimer’s Disease. Dr. Zipser is currently Professor Emerita in the Department of Physiology at Michigan State University where she is working on developing a therapeutic reagent again cancer.

In 1980 Birgit Zipser persuaded Susan Hockfield, a postdoctoral fellow at UCSF to join the scientific staff at the Cold Spring Harbor Laboratory as a Senior Staff Investigator. The Neurobiology group was together until 1985. Sue Hockfield left Cold Spring Harbor in May 1985.Dr. Hockfield would join Yale in 1985 and became a dean of its graduate school and later as provost. From 2004-2012 she served at the 16^th president of MIT, most notably the first female president of the institute.

 Anne Lutz worked at the Carnegie Institution of Washington Station for Experimental Evolution from 1905-1910. While George Shull was shuttling between California and Cold Spring Harbor, the research on genetics of plants was in the capable hands of Anne Lutz. Trained as a cytologist, she carried out important cytological studies and hybridization experiments in plants. Her most notable finding was that Hugo de Vries gigas mutant of Oenothera had doubled the number of chromosomes per cell as compared with the wild type plant. This was not a gene mutation of the kind Thomas Hunt Morgan studied in drosophila. This condition called polyploidy  gave Oenothera traits non-Mendelian patterns  inheritance which partly accounted for the strange behavior in which de Vries based his book “Mutationstheorie”. The importance of this work was recognized immediately. Eminent Cytologist  E.G. Conklin called this an “epoch” making result because it showed that mutations could be due to differences in chromosome number as well as intrachromosomal mutations. After a falling out with Laboratory Director Charles Davenport, she was asked for her resignation in 1910.

Barbara McClintock received her PhD in Botany from Cornell University in 1927, and accepted a full-time research position at the Carnegie Institution of Washington Department of Genetics, Cold Spring Harbor Laboratory in 1941.  A pre-eminent cytogeneticist, she developed the first maize genetic linkage map, demonstrated the roles of centromeres and telomeres, and uncovered genetic cross-overing during meiosis.

In 1944, in recognition of her prominence in the field of genetics during this period, McClintock was elected to the National Academy of Sciences—only the third woman to be elected. That same year, she became the first female president of the Genetics Society of America. She was elected its vice-president    in 1939. She was the first woman to be awarded the National Medal of Science.  She received the Louis and Bert Freedman Foundation Award and the Lewis S. Rosenstiel Award in 1978.  In 1981, she became the first recipient of the MacArthur Foundation Grant, and was awarded the Albert Lasker Award for Basic Medical Research the Wolf Prize in Medicine and the Thomas Hunt  Morgan Medal by the Genetics Society of America. In 1982, she was awarded   the Louisa Gross Horwitz Prize from Columbia University for her research in the "evolution of genetic information and the control of its expression.” Most notably, she received the Nobel Prize for Physiology or Medicine in 1983, the first woman to win that prize unshared, credited by the Nobel Foundation for discovering "mobile genetic elements.”            Source: CSHL Archives.

Anna Marie Skalka was a postdoc in Alfred Hershey’s laboratory from 1964-69. Skalka, along with Elizabeth Burgi and Hershey, were the core of the Lambda research group at the laboratory. In Hershey’s group Skalka worked on studying aspects of Lamba and T-5. Her work led to discoveries about the organisms’ replication. She completed her Ph.D. at New York University Medical School in 1964 and came to Cold Spring Harbor Laboratory to continue her graduate work on bacteriophage under Hershey. In 1969 she left for the Roche Institute for Molecular Biology and eventually she turned her attention to retroviruses. Dr. Skalka is now Senior Vice President for Basic Science and director of the Institute for Cancer Research at the Fox Chase Cancer Center in Philadelphia.  At Fox Chase, she studies molecular aspects of retroviral replication and hopes to uncover mechanisms of retroviral DNA integration. She has become interested in virally coded integrase, which catalyzes the integration of retroviral DNA into the host cell’s genome. Considering that stable integration of viral DNA into the host cell genome is essential for replication of retroviruses, her studies are important in developing antiviral drugs to treat AIDS.                                                                                                

Source: CSHL Archives

Marja Timmermans is a biologist who studied first in the Netherlands and then in the USA.  1998, Timmermans came to Cold Spring Harbor Laboratory and, in 2001, she was offered a position as assistant professor. She was a full professor from 2009 to 2015.  While at Cold Spring Harbor, Timmermans contributed significant research to her field, uncovering discoveries that have earned wide acclaim. This work includes explanations of important mechanisms of leaf development and the effect of small RNA molecules on leaf polarity. She is also on the editorial boards of several scientific journals and on the selection board of the National Science Foundation amongst others. In April 2015, Dr. Timmermans began her Alexander von Humboldt Professorship at the Centre for Plant Molecular Biology (ZMBP) at the University of Tübingen.

Source: https://www.cshl.edu/news-and-features/dr-marja-timmermans-plant-geneticist-begins-alexander-von-humboldt-professorship-in-germany.html

Eileen White received her Bachelor of Science degree from Rensselaer Polytechnic Institute followed by a Ph.D. in Biology from SUNY Stony Brook. She came to Cold Spring Harbor Laboratory as a Damon Runyon Postdoctoral Fellow in the laboratory of Dr. Bruce Stillman from 1983-1985, and then as a Staff Investigator from 1986-1990.  Here she discovered that one of the oncogenes of the DNA tumor virus adenovirus encoded an inhibitor of programmed cell death that was a viral homologue of Bcl-2. She went on to establish that oncogene activation that deregulates cell growth also activates apoptosis, and that inhibition of apoptosis is an important cancer-promoting function. These findings revealed roles for the p53 tumor suppressor in activating apoptosis and suppressing cancer and the Bcl-2-related anti-apoptotic proteins in blocking apoptosis and promoting cancer.

Dr. White is currently Associate Director for Basic Science Rutgers, Cancer Institute of New Jersey.

Mary Osborn Weber was educated at Cheltenham Ladies' College and Newnham College, Cambridge where she graduated in Mathematics and Physics in 1962. She went on to take masters in biophysics at Pennsylvania State University in 1963 and a PhD on mutagenesis in nonsense mutations in bacteria, awarded by Pennsylvania State University in 1972.

Dr. Osborn did postdoctoral research at Harvard University with Nobel Laureate James Watson. She conducted research at the Laboratory of Molecular Biology, Cambridge, UK before moving to the Cold Spring Harbor Laboratory in 1974 with her husband, Klaus Weber.  While at CSHL, Mary studied the effects of temperature sensitive mutants of the SV40 gene A on the virus’s ability to transform rat embryos.

Dr. Osborn relocated to the Max Planck Institute for Biophysical Chemistry in 1975, where she still maintains an office.   Source: https://en.wikipedia.org/wiki/Mary_Osborn

Evelyn Witkin began graduate studies with Theodosius Dobzhansky at Columbia University in 1941, which sparked her interest to change from Drosophila genetics to bacterial genetics. In the summer of 1944 at Cold Spring Harbor, she isolated a radiation-resistant mutant of E. coli.  She became a full-time staff scientist at Cold Spring Harbor in 1945. Witkin was awarded her Ph.D. in 1947 and remained at C.I.W. Department of Genetics until 1955. 

Dr. Witkin was elected to the National Academy of Sciences in 1977.  Among many other awards and honors, she was awarded the 2015 Lasker Award, the 2000 Thomas Hunt Morgan Medal, and was presented with the National Medal of Science in 2002.