Tenure-Track Investigator
National Institute of Diabetes and Digestive and Kidney Diseases
Ph.D.,Weizmann Institute of Science, Rehovot, Israel
Postdoctoral Fellowship: Carnegie Institution of Washington, Baltimore, MD
Hometown: Jerusalem, Israel



Where are you from? My name is Orna Cohen-Fix and I was born in Pittsburgh, PA, but I grew up in Jerusalem, Israel.

Please list the degrees that you have earned, the institutions where you earned them, and your academic specialty(ies) and thesis title/postdoctoral research emphases. B.Sc. Tel Aviv University, Tel Aviv, Israel
M.Sc. The Weizmann Institute of Science, Rehovot, Israel (with Dr. Zvi Livneh)
Ph.D. The Weizmann Institute of Science, Rehovot, Israel (with Dr. Zvi Livneh). Thesis title: The biochemical analysis of UV mutagenesis in Escherichia coli
Postdoctoral fellowship: the Carnegie Institution of Washington, Baltimore, MD (with Dr. Doug Koshland). Main focus: Cell cycle regulation in budding yeast. Funded by Human Frontiers Science Program Organization long-term research fellowship, and by an NIH postdoctoral fellowship.

Briefly describe the research in which you are currently involved. My lab works on cell cycle regulation in budding yeast. In particular we are interested in regulatory pathways that drive cell division and in surveillance mechanisms, also known as checkpoint pathways, that stop cell cycle progression when cellular components malfunction or become damaged. In mammalian cells the inactivation of these surveillance mechanisms can lead to cancer. The budding yeast is a wonderful system for studying these questions because it lends itself to genetic, biochemical and cytological manipulations. At the same time, many of the processes that drive cell cycle progression are conserved throughout evolution. We are now focusing our attention on the regulation of mitosis, and we are trying to understand how the different regulatory proteins are activated and inactivated. A new project in the lab is aimed at identifying proteins that are involved in yeast nuclear architecture, namely the proteins that determine nuclear structure and define sub-nuclear domains.

How did you develop an interest in this area? As a graduate student I developed an interest in various aspects of DNA metabolism. I then sought a eukaryotic experimental system that would allow me to combine genetics and biochemistry, and the obvious choice was budding yeast. In the course of my postdoctoral work I came to appreciate the beauty and sophistication of the intricate regulatory mechanisms that drive cell cycle progression in general, and chromosome segregation in particular, and I decided to continue this line of research in my own lab. More recently I've developed an interest in nuclear structure, the determinants of which are largely unknown, and yet it is an integral part of many biological processes, such as gene expression, DNA replication and DNA repair.

Can you describe a typical work day for you at the NIH? The great thing about my job is that there really isn't a typical day. My day is defined by the experiments I do, by the informal interactions I have with my lab members and colleagues, and by the seminars and lectures I attend several times a week. There are days when my time is consumed by a demanding experiment. On others I spend hours going over data and hypotheses with my postdocs, trying to make sense of unexpected results and plan the next few steps. Writing is also a big part of my job and that includes writing manuscripts and reviews, peer reviewing for scientific journals and various NIH-related forms.

Has your experience at the NIH changed your research interests? My experience at the NIH has not changed my research interest, but the resources I have here and the freedom to pursue my ideas have allowed me to venture into the new field of nuclear morphology.

Have trainees, whether summer or postdoctoral, played a role in your research? The great thing about trainees is that they force you to think; in order to explain a biological problem one first must understand it. Trainees come from different backgrounds and with different experiences, and they often have a novel way of looking at things. Sometimes it is the naïve question that makes one look at things from a new angle, often revealing aspects of the problem that were not appreciated before. Most trainees come with little experience in my area of research but with time they develop their own niche and original ideas. There is something magical about watching someone transform into an independent scientist, and as a mentor I feel great pride when my postdocs or students do well.

Do you have interests outside of the NIH that you would be comfortable describing to readers of the Research and Training web site? Most of my non-science time is taken up by my two kids, Tal (age 10) and Jonathan (age 8). Through them I discovered that I like to work with kids, and in the past few years I've been involved in leading Tal's girl scout troop and in being an assistant soccer coach (the latter with marginal success). I must admit that getting the approval of a bunch of 10 year-olds is sometimes more challenging than getting a scientific idea across. It's not easy to combine career and family but it's incredibly rewarding and worth every bit of effort (and lack of sleep).

Tenure-Track Investigator
Genetics Branch, National Cancer Institute
B. S. and M. S., Abasaheb Garware College, University of Pune, India
Ph. D. University of Tennessee, Knoxville, TN
Postdoctoral Research, Johns Hopkins School of Medicine, Baltimore, MD
Pune, India



B. S. and M. S., Abasaheb Garware College, University of Pune, India

Ph. D. University of Tennessee, Knoxville, TN (Mentor, Dr. Jeffrey Becker). Research objective: characterization of fluid phase endocytosis and peptide transport system in the opportunistic pathogen, Candida albicans.

Postdoctoral Research, Johns Hopkins School of Medicine, Baltimore, MD (Mentor, Dr. Philip Hieter). Research objective: identification of molecular determinants of genome stability in budding yeast and their evolutionarily conserved human homologs.

I was born and grew up in Pune, India which is 160 miles from Mumbai. I came to the United States 18 years ago to pursue my graduate education and career goal of establishing a research laboratory. I still recall the day when I first saw a living cell under the microscope, an observation that piqued my research interest in how cells divide and propagate. I quickly learned that the process of faithful transmission of chromosomes was the key factor that determined genome stability. Since budding (bakers) yeast offers the 'AWESOME POWER OF GENETICS,' it became the obvious model system of choice. Hence, I sought a postdoctoral research laboratory that offered me an excellent opportunity to initiate and continue this long-standing research interest.

I have continued my research as a tenure-track investigator in the Genetics Branch at the National Cancer Institute of the NIH. Research in our laboratory focuses on defining the molecular determinants of faithful chromosome segregation and cell cycle checkpoint responses in budding yeast. These studies are important as most of the genetic information that provides the blueprint for an organism is contained in the chromosomes of its cells. The maintenance, replication, and segregation of these chromosomes are controlled by the mitotic cell division cycle. Checkpoints ensure the sequential execution of the events in the cell division cycle. Not surprisingly, errors in chromosome segregation have dramatic consequences and have been implicated in cancer, aging, and congenital birth defects. Hence, we are also developing and implementing yeast/human cross-species approaches to identify evolutionarily conserved genes in these pathways. The relevance of our studies is reinforced by the fact that, to date, about one-third of all human disease-associated genes have functional homologs in yeast, including mammalian homologs of yeast genes required for chromosome segregation and checkpoint function. Detailed analysis of chromosome segregation and checkpoint responses in yeast will help us understand how these processes operate successfully (health) or fail to operate (disease) in humans. For our studies, we use a combination of genetic, cell biology, biochemistry, and genomics approaches. For the latter, we have constructed a whole genome array of budding yeast for studies on gene regulation, gene function, chromosome structure, and the identification of Non-Annotated ORFs (NORFs). We are particularly interested in the NORFs that represent small genes not yet annotated by genome sequencing efforts. We have previously reported the biological significance of one of these NORFs, encouraging us to pursue the characterization of others.

I have immensely enjoyed the past few years here at NIH, and especially being a part of the National Cancer Institute. The leadership at every level including the Genetics Branch with which I am affiliated has been extremely supportive of our program. This has allowed me to explore areas of interest and use approaches that would be otherwise difficult in other places. The flexibility has fostered many fruitful collaborations with investigators both within and outside the NIH to pursue whole genome approaches in defining new genes and their function. The NIH campus offers, by far, the maximum resources, seminars, and workshops conducted by reputable leaders in the field. It may be appropriate to say that at the NIH 'sky is the limit' in terms of opportunities to broaden one's horizon and network, and to grow as a scientist.

The trainees, including summer interns, postbaccalaurate and postdoctoral fellows, become a major driving force in the laboratory. Each individual brings different strengths to the group, and we all benefit from this diversity. In turn, the laboratory group plays a pivotal role in mentoring a trainee to address the biological problem under investigation and pursue approaches with possible interpretations of the data. The latter is one of the most stimulating parts of my job as I learn to view the research problem from someone else's viewpoint. These interactions are very rewarding. A testimony to this is the initiation during the past year of a new project based on the observation and intellectual pursuit of a summer intern. I also enjoy teaching, a passion that is, in part, satisfied by mentoring the research program in our laboratory. In addition, since NIH is not a typical academic setting, I volunteer some of my time to give talks at workshops/courses at other institutes or colleges.

No typical workday really exists for me here at NIH. Every day is somewhat different in terms of prioritizing responsibilities. The daily activities include interactions with my trainees, writing (manuscripts, review articles, progress and site visit reports), attending seminars, networking, and participation in various faculty interest groups. My first priority is the research effort in the laboratory, which includes conducting some of my own experiments and mentoring the fellows/trainees in the laboratory. The best part of this involves the discussions of hypothesis/models and the possible experiments to be done, as well as interpretation and analysis of the data generated from such efforts. I have learned over the years that one has to keep an open mind when interpreting data and be prepared to accept the 'story' that the 'cell' is trying to tell rather than forcing the data to fit the hypothesis.

Research is extremely rewarding, especially when your group thrives to meet the challenges of defined objectives. However, family, friends, and cultural heritage are also part of my priorities. Over the years, I have balanced my professional career with family activities and traveling agendas. During my travel to different parts of the world I have witnessed and learned about the historical, cultural, wildlife, and natural beauty that each land has to offer.