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HIV-Susceptible Mice  In a May 2013 issue of PLoS ONE, Dr. Harris Goldstein and graduate student Kieran Seay report their development of a genetically engineered mouse that can be used to study HIV. Since a critical step in testing new drugs is to demonstrate effectiveness in mice; the researchers first had to overcome a critical obstacle: Mice cannot be infected by the virus. HIV infects by binding to and entering molecules via the proteins CD4 and CCR5, which are present on the cell surface of human immune cells. The virus then utilizes an internal protein, cyclin T1, to make copies of itself. The researchers were able to genetically engineer a mouse with the human copy of these critical genes, rendering the new mouse model susceptible to HIV infection. This “humanized” mouse model therefore provides a new way to conduct essential preclinical testing of HIV therapies to accelerate discovery of novel treatments. Dr. Goldstein is professor of pediatrics and of microbiology & immunology. He also is the Charles Michael Chair in Autoimmune Diseases and director of Einstein’s Center for AIDS Research.

Wednesday, July 31, 2013
 

HIV Intervention  Dr. Betsy Herold and her colleagues have been awarded $12 million over five years from the National Institute of Allergy and Infectious Diseases for their novel approach to HIV prevention. Effective HIV preventatives have remained elusive due to difficulties with adherence and biological differences in how drugs are distributed to sites of HIV acquisition. Dr. Herold has proposed that drug development begin with extensive assessments of these factor using animal models and clinical samples. The investigators will then apply their findings to further optimize an intra-vaginal ring that delivers a more potent combination of drugs than current gel products and ensures appropriate dosage and targeting of tissues, while also overcoming issues of patient adherence to strict dosing regimens. Dr. Herold is professor of pediatrics (infectious diseases), of microbiology & immunology and of obstetrics & gynecology and women’s health. Co-investigators at Einstein include Dr. Marla Keller and Pedro Mesquita. The Einstein team will work with collaborators at other institutions, including the University of Utah, Northwestern University, Johns Hopkins, the Centers for Disease Control and Prevention, University of Washington, and Kenyatta National Hospital in Nairobi, Kenya.

Wednesday, July 31, 2013
 

All in the Family  In the May 7, 2013 issue of the journal StructureDr. Andras Fiser , Dr. Steve Almo and former graduate student Dr. Rotem Rubenstein describe the brotherhood algorithm, a new computational method that groups proteins into functionally related families.  Based on the principle that “if my brother is your brother then we must also be brothers,” the method identifies and clusters families of proteins by shared similar proteins between any two candidates.  Using this method, they identified and, through experiments,  subsequently verified new members of the nectin/nectin-like protein family, which have key roles in mediating the immune response. The brotherhood algorithm can be used to discover new functional relationships among cell surface-attached immunoglobulin proteins; these proteins are common therapeutic targets for developing treatments for infectious diseases, cancer, and autoimmune diseases.  Dr. Fiser is professor of systems and computation biology and of biochemistry; Dr. Almo is professor of biochemistry and of physiology & biophysics

Wednesday, July 31, 2013
 

Mutant G Proteins and Human Disease  This week's New England Journal of Medicine (NEJM) published an editorial on G proteins written by Dr. Allen M. Spiegel, Einstein's Marilyn and Stanley M. Katz Dean. Members of the G protein family couple activation of a class of transmembrane receptors termed GPCRs to signaling pathways that regulate key cellular processes. GPCRs are activated by a diverse array of extracellular signals including hormones, neurotransmitters and photons of light. Dr. Spiegel's editorial accompanied the publication of a research paper and letter reporting that mutations that inactivate or activate a particular G protein cause hypercalcemic and hypocalcemic disorders, respectively. Previous studies had shown that these disorders can also result from mutations in the gene encoding a GPCR activated by extracellular calcium. Dr. Spiegel noted that the present work expands the list of diseases caused by mutant G proteins beyond those originally described by his and other labs. (Subscription may be required)

Wednesday, July 31, 2013
 

Structurally Sound  In the June 4 issue of Structure, Drs. Vern Schramm, Steven Almo and Antti Haapalainen report their use of crystallography – a method used to determine molecular structures by examining them in crystalline form – to identify novel inhibitors of a key enzyme of the bacteria Salmonella enterica.  This enzyme, called MTAN (MTA/SAH nucleosidase), is responsible for metabolism of the amino acid methionine and is only expressed by bacteria, making it an ideal target for developing antibiotics.  Drs. Schramm and Almo analyzed the crystal structure of MTAN and used this structural information to develop rational design of inhibitors that bind to the enzyme very strongly, identifying new possible antibiotics against S. enterica as well as a method that can be used to develop inhibitors of other bacterial targets. Dr. Schramm is professor and chair of biochemistry and the Ruth Merns Chair in Biochemistry; Dr. Almo is professor of biochemistry and holds the Wollowick Family Foundation Chair in Multiple Sclerosis and Immunology; Dr. Haapalainen is a postdoctoral fellow in the Schramm lab.

Wednesday, July 31, 2013
 

PREP-ing for the Future  Dr. Myles Akabas has been awarded a $1.4 million grant over four years from the National Institute of General Medical Sciences. The grant will support the establishment of a Post-Baccalaureate Research Education Program (PREP) at Einstein. The racial and ethnic diversity of the American population is not reflected in the biomedical workforce or faculty at research universities and medical schools; PREP provides underrepresented minority college graduates with a year-long intensive research experience that will allow them to be competitive applicants to rigorous Ph.D. and M.D.-Ph.D. programs. PREP will combine didactic and experiential learning components, community outreach through visits to local Bronx high schools and mentorship at all levels. Dr. Akabas is director of the Medical Scientist Training Program (MSTP) at Einstein, as well as professor in the departments of physiology and biophysics, neuroscience and medicine. PREP is co-directed by Drs. Victoria Freedman, associate dean of graduate studies, and Genevieve Neal-Perry, associate dean for diversity mentoring.

Wednesday, July 31, 2013
 

Focus on Cataracts  The National Eye Institute has awarded Dr. Ales Cvekl a $2.2 million renewal grant, over four years, for his investigations into the formation of ocular lens through studies of its major protein component, the aA-crystallin. Because loss of expression of aA-crystallin leads to cataract formation, the researchers aim to determine the molecular mechanisms that regulate the protein’s expression. Lens cataract is a major cause of blindness worldwide. Age-related cataracts generally develop after 40 years of age; increasing life expectancy is expected to increase the prevalence of cataracts. Current treatment of cataract requires surgery to replace the opaque lens with an artificial lens. In this project, the researchers hope to identify strategies that might delay the onset of cataracts, ultimately decreasing the number of surgeries needed as well as vision care costs. Dr. Cvekl is professor and vice chair for research of ophthalmology & visual science and professor of genetics. He also is the Max Berger Chair in Ophthalmology.

Wednesday, July 31, 2013
 

The Mighty Macrophage  In the April 2013 issue of Nature, Dr. Jeffrey Pollard published a scientific review on the role of macrophages in development, homeostasis (the maintenance of balance within a system), and disease, which was featured on the cover as their “Cell for All Seasons.”  Macrophages are immune cells that have primarily been thought to be controllers of infection; by engulfing invading microbes and orchestrating immune responses. Dr. Pollard’s review focuses on emerging evidence – from his lab and others – that, in addition to their immune functions, these cells play important roles in development and homeostasis. Furthermore, most of these cells do not arise from bone marrow, where other immune cells typically do, but rather from yolk-sac progenitors during embryo development. This new information about these important cells could facilitate development of therapeutic interventions to treat obesity, cancer, and degenerative diseases.  Dr. Pollard is professor of developmental and molecular biology and of obstetrics & gynecology and women’s health.  He is also director of the Center for Study of Reproductive Biology and Women’s Health; and the Louis Goldstein Swan Chair in Women’s Cancer Research.

Wednesday, July 31, 2013
 

Regulating Human Immune Response­­  Dr. Xingxing Zang, Dr. Matthew Scharff,  and colleagues published a study in the June 11, 2013 issue of Proceedings of the National Academy of Sciences USA, describing a new pathway that inhibits human T cell functions. T cells are key part of the immune system and the discovery may aid the development of new therapies for treating cancer, autoimmune disorders, infection and transplant rejection; it also may aid the design of better vaccines. The researchers identified a protein, HHLA2, as the newest  member of the B7 family of proteins; B7 proteins bind to receptors on the surface of T cells and either inhibit or activate the T cell response. The researchers demonstrated that exposing human T cells to HHLA2 inhibited proliferation and protein production, suggesting that this pathway may be a potent regulator of human immune responses. Dr. Zang is associate professor of microbiology & immunology, and Dr. Scharff is distinguished professor of cell biology.  Einstein has filed for patent protection on this technology. It's available for licensing.

Wednesday, July 31, 2013
 

Improving Screening  Dr. Howard Strickler has received a $2.4 million grant over four years from the National Cancer Institute to identify molecular methods for improving cervical cancer screening in HIV-positive women. These women a have an increased incidence of cervical pre-cancer and cancer and, at each doctor visit, nearly one-third of them experience abnormal Pap tests (the screening tool used to detect these conditions). Because many abnormal Pap tests are false positive, leading to unnecessary follow-up procedures that are costly and unpleasant to undergo, Dr. Strickler’s study will assess whether new molecular screening methods can provide more accurate results among this patient population. Improving accuracy of cervical cancer screening tests through the use of these molecular assays, either alone or in combination with Pap tests, could possibly improve clinical care for women with HIV, while reducing the burden on patients and the health care system. In addition, a related study by Dr. Strickler and colleagues published last year in the Journal of the American Medical Association was picked recently by the Epidemiology & Genomics Research Program of the NCI as a “Research Highlight.” Dr. Strickler is a Harold and Muriel Block Chair in Epidemiology & Population Health, as well as professor of epidemiology & population health.

Wednesday, July 31, 2013
 
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