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Exploring HAAF pathways  Dr. Ilan Gabriely has been awarded $1.8 million over five years from the National Institute of Diabetes and Digestive Kidney Diseases. The grant will allow him to continue his investigations into the mechanisms responsible for autonomic failure after repeated episodes of hypoglycemia (low blood glucose levels). Patients with type 1 diabetes are susceptible to develop this condition due to defects in hypoglycemia counterregulation. Previously, Dr. Gabriely’s team demonstrated that hypoglycemia-associated autonomic failure (HAAF) could be prevented in healthy volunteers and in individuals with type 1 diabetes, by blocking their opioid receptors with naloxone. The researchers hope to determine whether a common mechanism exists between the opioid receptor pathway and the adrenergic pathway, in instances when HAAF occurs. Additionally, they will conduct a clinical trial examining the efficacy of chronic opioid receptor blockade, in preventing HAAF in patients with Type 1 diabetes. Dr. Gabriely is associate professor of medicine.

Wednesday, July 31, 2013
 

Detecting the Elusive ‘Ylide’  Ylides, molecules containing two opposing charges on adjacent atoms, have been proposed as intermediates in biochemical reactions, but until now there was little evidence supporting this theory. In a study appearing in Nature’s May 15 online edition, Drs. Jungwook Kim and Steven Almo, and colleagues describe a ylide intermediate — formed from the biomolecule SAM (S-adenosylmethionine) — during biosynthesis of the newly identified metabolite Cx-SAM. The group subsequently demonstrated that Cx-SAM is used to generate the modified nucleotide5-oxyacetyl uridine (cmo5U) on bacterial tRNAs, which is required for efficient processing of the genetic code. While determining the X-ray crystal structure of an enzyme required for the biosynthesis of cmo5U, the researchers discovered Cx-SAM — a SAM molecule with a carboxylate (CO2-) group attached, in the enzyme’s active site. They theorized that this metabolite was generated from SAM via a series of biochemical reactions involving the formation of a ylide, and then tested several compounds that led to their discovery that prephenate (an aromatic amino acid precursor) generated Cx-SAM, thereby providing compelling evidence for the existence of the ylide intermediate. Dr. Kim is an associate of biochemistry and Dr. Almo is professor of biochemistry and of physiology & biophysics. Dr. Almo holds the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology.

Wednesday, July 31, 2013
 

B7x-cellent — In the March 1, 2013 issue of the Journal of Immunology, Drs. Xingxing Zang, Yael Abadi, and Hyungjun Jeon report a role for the immune regulatory molecule B7x in promoting the spread of cancer (metastasis). B7x inhibits the immune response and increased levels on tumors in cancer patients has been associated with poor clinical outcomes and death. Using a mouse model of metastatic breast cancer, the researchers found that removal of B7x signaling enhanced the anti-tumor immune response, which resulted in a decrease in tumors and enhanced survival. Cancer is the leading cause of death worldwide and targeted treatments for metastasis are critical to improving survival. The findings suggest that blocking B7x could offer a therapy that harnesses the power of the immune response to treat metastatic cancers. In related news, the journal OncoImmunology has invited Dr. Zang to write an “Auto-Commentary” on this work, and the Department of Defense’s Prostate Cancer Research Program has selected Dr. Zang's cancer immunology research to be highlighted in its program materials that communicate buzz-worthy research to Congress and other stakeholders. Dr. Zang is assistant professor of microbiology and immunology. Dr. Jeon is a research fellow in the Zang lab, and Dr. Abadi is a Ph.D. student who successfully defended her thesis recently.

Wednesday, May 01, 2013
 

Metabolic Transformation — Dr. Antonio Di Cristofano has been awarded a $1.6 million grant over five years from the National Cancer Institute to study the role of the protein, PI3K, in the transformation of cells into tumor cells. Cancer cells have a characteristic metabolism that is different from normal cells. The researchers previously demonstrated that increased activation of PI3K in epithelial cells of the thyroid produces a metabolic profile similar to that of cancer cells — although preceding the transformation process and acting through a previously unknown pathway. This grant will allow the researchers to test the hypothesis that PI3K coordinates changes in gene expression that alter cellular metabolism, thereby creating an environment that favors transformation. The results from this research could help develop innovative targeted approaches aimed at selectively disrupting tumor growth while preserving metabolism in normal cells. Dr. Di Cristofano is associate professor of developmental & molecular biology and of obstetrics & gynecology and women’s health.

Wednesday, January 30, 2013
 

Macrophages and Metastasis — Dr. Jeffrey Pollard has been awarded a $2.1 million grant over five years from the National Cancer Institute. The funding will support research to define the role of a particular type of cell of the immune system, macrophages, on the ability of tumor cells to spread from the initial site to other parts of the body. This process, known as metastasis, is the major cause of cancer death. The research will focus specifically on how macrophages promote the growth and survival of tumor cells in bone marrow and lungs, the main sites of breast cancer metastasis. Elucidating the mechanisms by which macrophages influence the establishment of tumors in bone and lung could result in the development of new therapeutic agents to fight metastatic breast cancer, the most common malignancy in women. Dr. Pollard is professor of developmental & molecular biology and of obstetrics & gynecology and women's health, director of the Center for Study of Reproductive Biology and Women's Health  and the Louis Goldstein Swan Chair in Women's Cancer Research.

Tuesday, January 29, 2013
 

Living Colors — Dr. Robert Singer and colleagues have developed a new technique for simultaneously monitoring the expression of two genes inside living cells. In research published in the February 2013 issue of Nature Methods, the scientists were able to count the number of mRNA molecules transcribed by two different alleles  of a yeast gene by attaching differently-colored fluorescent proteins to each, or “tagging” them. The labeling effort in this study, combining one well-established tag, MS2, and one new tag, PP7, revealed that a population of identical cells exhibits variation in gene expression levels. This phenomenon may be evolutionarily advantageous and may also help explain why genetically identical twins often exhibit slight differences. The publication presents a methodology that will have countless uses in the field of RNA biology.  First author, Sami Hocine is a Ph.D. student in the lab of Dr. Singer, who is professor and co-chair of anatomy & structural biology, professor of neuroscience and of cell biology and co-director of the Gruss-Lipper Biophotonics Center. Dr. Jeffrey Chao and Dr. Daniel Zenklusen, former postdoctoral research associates in anatomy & structural biology, contributed to the research.    

 

Friday, January 25, 2013
 
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