T H E   N I H   C A T A L Y S T      S E P T E M B E R  –  O C T O B E R   2003


by Peter Kozel and Celia Hooper


This year’s Summer Poster Day (August 7), the annual exhibition of their research by students in NIH summer research programs, attracted so many participants it had to be divided into morning and afternoon sessions. Following are but eight of the record 484 posters presented throughout the day.

Double Take: Seth (left) and Joshua Cohen attend ther same medical school but worked in different NIH labs this summer

Angiogenesis Inhibition

Many kinds of tumors secrete molecules that promote the formation of new blood vessels, allowing them to continue their rapid growth. NIDCD investigators Zhong Chen and Carter Van Waes had previously observed high levels of hepatocyte growth factor in patients with head and neck squamous cell carcinomas. Brian Worden, an HHMI scholar working in that lab the past year, identified Egr-1 as a potentially important transcription factor in the expression of platelet-derived growth factor and vascular endothelial growth factor.

Continuing Worden’s work, Joshua Cohen succeeded in elucidating the Egr-1 signaling pathway that turns on these two angiogenic growth factors. He also showed that antisense oligos to Egr-1 inhibited expression of Egr-1 in a squamous cell carcinoma cell line.

This type of head and neck tumor is often detected too late for the usual therapeutic regimen to be effective; it’s hoped that blocking Egr-1 will eventually prove clinically useful, Cohen notes.

Cohen, a second-year medical student at Northwestern University Medical School in Chicago, said that working at NIH has been an "amazing" experience. "You study and read about stuff in medical school. Here you get to work with the people doing that research." He thanked by name his preceptors Van Waes and Chen—and everyone else in the lab—for teaching him how to carry out experiments. His fate, he says, is now sealed: "I have to stay in research."—P.K.

Stem Cell Platforms

Perhaps it is fitting that Seth Cohen, who declares himself the better-looking one of two identical twins working at NIH this summer, also got the sexy research topic—stem cells. Cohen, working with NIAMS mentors Wan-Ju Li and Rocky Tuan, cultured mesenchymal stem cells from adult human bone marrow.

His goal was to compare growth of the cells on the usual flat surfaces to growth on biodegradable, potentially implantable 3-D nanofibers made of poly(e)caprolactone (PCL). The results—equal or slightly superior proliferation on the PCL film—bode well for the possibility of someday implanting the nanofiber disks, loaded with stem cells, as frameworks for regrowing cartilage. The cells on nanofibers also showed greater predilection for calcium mineralization, beginning this differentiation into osteocytes on day 1 vs. day 4 for the monolayer.

Like his twin, Cohen is a second-year medical student at Northwestern University in Chicago. He came to NIH—"The Big House"—for its world-class research and researchers and would like to combine research with medical practice in his career.C.H.

Michael DiPrima

A Model Receptor

Michael DiPrima says the most important thing he learned at NIH this summer was "how to learn." A senior this fall in Carnegie Mellon’s biophysics program (Pittsburgh, Pa.), DiPrima built upon his biophysical coursework to refine a model for the GluR6 glutamate receptor. Upon binding this excitatory neurotransmitter, the receptor opens, allowing ions to enter a postsynaptic neuron.

Mark Mayer’s lab in NICHD, where DePrima did his work, is studying the mechanisms of ligand binding to GluR6 based on X-ray crystallographic diffraction patterns (see story this issue). These patterns are translated using computer algorithms into atomic models—but you have to know which algorithm to use.

DiPrima’s project was to generate a model using one software package and compare it to a model his preceptor created using a different program. When DiPrima’s model proved more accurate, the student became the teacher: He spent his last week here teaching Mayer how to use the better computer program! DiPrima hopes to continue teaching after graduate training in biophysics. —P.K.


Anna Binstock
Bipolar Comorbidity

Studies in adults show that anxiety disorders are prevalent in those with bipolar disorder (BPD). Anna Binstock, working with NIMH’s Ellen Leibenluft and Daniel Dickstein, sought to learn whether that would be the case in children as well. Binstock examined medical records of young patients with BPD, collected as part of a larger, ongoing study of pediatric BPD.

Most of the 31 patients in the sample displayed anxiety, a co-morbidity rate in line with the 25–90 percent range reported in adults. Moreover, children with both BPD and anxiety were more functionally impaired, with an earlier age of BPD diagnosis and more frequent psychiatric hospitalizations. Though not a focus of the study, Binstock notes that treatment of these patients may be tricky, because standard antianxiety agents may exacerbate BPD symptoms.

A sophomore at Cornell University, in Ithaca, N.Y., Binstock plans to be a pediatric psychiatrist. She enjoyed her experience here shadowing clinicians as they interacted with children and seeing how psychiatric diseases manifest themselves. —P.K


Rhonda Moore
Sights and Smells

Rhonda Moore is a unique participant in the summer research program: She has a Ph.D. in anthropology. She was pursuing postdoctoral research at the M.D. Anderson Cancer Center in Houston when she caught the neuroscience bug.

Working in Alan Koretsky’s lab in NINDS this summer, she used manganese as a contrast agent to enhance the visualization of the rat olfactory system. She anesthetized and intubated rats, applied a manganese chloride solution to their noses, and placed the animals inside an MRI instrument. Manganese reduces T1 relaxation time, causing positive contrast enhancement in tissues where it accumulates. Future studies will determine which portions of the olfactory bulb respond to specific odorants.

Moore notes that while this particular contrast agent may not be as useful in human brain studies, it is an invaluable means of studying olfaction in knockout animals that are models for human disorders. Now committed to mastering various imaging modalities, she says a key factor in her selection of a graduate biology program will be the availability of an MRI system.. —P.K


Sunil Patel (left) and Karl Dauphinais
Fishing for Folate Effects

Eating w-3 fatty acids from fish can ameliorate risk factors for heart disease, but levels of consumption of fish are low in the United States. Working with NIAAA investigator John Umhau, medical students Sunil Patel and Karl Dauphinais set out to explore whether folate sup-plementation might increase the absorption of dietary w-3 fatty acids, especially of the long-chain DHA form—a possibility suggested by a correlation between red blood cell folate levels and plasma levels of DHA in rats.

Using human serum samples collected for another study in the lab, they observed a similar correlation in humans. Interestingly, high levels of folate correlated with high levels of DHA, but not of other w-3 or w-6 fatty acids. They are proposing future studies to determine whether plasma DHA levels rise in people who take folate supplements.

Patel, a second-year medical student at Midwestern University, Chicago College of Osteopathic Medicine, at Downer’s Grove, Ill., wants to become a cardiologist and tackle the problem of sudden cardiac death. Being able to transform research findings into novel ways to treat patients, he says, "is the best way to practice medicine." Dauphinais, a fourth-year medical student at the University of Miami, will be starting an internal medicine residency and hopes to do clinical research as an adjunct to a practice that emphasizes preventive care and patient education.. —P.K


Enjoli Cooke (left) and mentor Peggy Zelenka
Signaling Surprises

Enjoli Cooke points proudly to her picture-perfect Western blots. The senior from St. John’s College in Annapolis, Md., says the most important thing she learned this summer in Peggy Zelenka’s NEI lab was the patience it takes to get clear data—even when they point to negative results. "It took two and a half months to get there," she laughs.

Cooke was following up on studies suggesting that epidermal growth factor (EGF) has different effects on cells at different concentrations. Using her lab’s immortalized rabbit lens epithelial cells, she exposed the cells to a range of concentrations of EGF, then looked at the response of the three key initial pathways set off by EGF signaling to see whether they responded differently from one another.

The beautiful theory—that the varying response of the cells to low vs. high EGF levels was due to different responses of the MAPK, PI3K, and PLC-g signaling pathways—is now threatened by an ugly fact. In Cooke’s experiment, all three pathways responded similarly, switching on and staying on from low concentrations to high. Cooke says more experiments are needed to put the theory to rest—and that her enthusiasm for molecular biology remains intact. She wants to pursue postbac studies in proteomics.. —C.H.


Zishuo Hu
Stem Cell Markers

Zishuo Hu, working with Tobi Limke and Mahendra Rao at NIA in Baltimore, has been in pursuit of useful markers that would distinguish neuronal stem cells in the subventricular zone (SVZ) of the embryonic mouse brain from cells in the ventricular zone (VZ) of the developing cortex. Other scientists have found transcription factors that distinguish VZ cells from more mature cells in the developing spinal cord.

Hu wanted to see whether these markers could be used in developing cortex but also sought extracellular markers that could be used to sort cells. Working with tissue from 16-day mouse embryos, Hu was foiled in his goal of distinguishing SVZ from VZ cells, but did come up with some nice markers that could be used to distinguish SVZ from VZ stem cells jointly from more differentiated surrounding cells. This preliminary work pointed to CD24 and PDGFRa (platelet-derived growth factor receptor–a) as non-VZ and SVZ cell markers, and Sox1 as a potential VZ and SVZ marker.

Hu says he greatly values this lab experience and learning that "science can be difficult and exciting at the same time." A sophomore at Brown University in Providence, R.I., he says he is strongly leaning toward a career in research..—C.H.


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