Roundup Of Roundups

The following research papers and grants of note were highlighted on the Einstein website in a section called "Research Roundup." You can explore all of the discoveries published in this special section of our website throughout the year by visiting the Research landing page of our website.

Deciphering the Hippocampus—The dentate gyrus (DG) is a part of the hippocampus that plays a key role in forming new memories. It receives information from many areas of the brain, transforms them into new patterns, and sends them to another part of the hippocampus. How the different cell types within the hippocampus communicate with each other is poorly understood. Pablo Castillo, M.D., Ph.D., has received a 5-year, $2.6 million grant to identify the properties of key hippocampal neurons—most notably granule cells and hilar mossy cells—that interact to create an excitatory circuit known to be involved in learning and epilepsy. Findings may shed light on information processing and memory encoding and reveal how dysregulation of this circuit may contribute to brain disease including epilepsy, anxiety, schizophrenia, and depression. Dr. Castillo is a professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences, and the Harold and Muriel Block Chair in Neuroscience at Einstein. (1R01NS113600)

Friday, September 06, 2019

Award for Patient-Oriented Opioid Research—The New York State Department of Health’s Empire Clinical Research Investigator Program (ECRIP) has awarded a two-year, $574,166 grant to the Montefiore/Einstein Center for Comparative Effectiveness Research (CCER). The CCER will look for ways to help patients with or at risk for opioid use disorder (OUD) achieve better outcomes. Led by Julia Arnsten, M.D., M.P.H., chief of the division of general internal medicine at Montefiore and Einstein, the CCER was established in 2013 to improve patient-centered health outcomes in urban, diverse, and underserved populations. The five projects funded by the new grant will include studies to see how medical cannabis compares with opioids for controlling chronic pain in people living with HIV; examine using medical cannabis for reducing opioid use in patients with head and neck cancer; assess strategies for safer opioid prescribing for patients with sickle cell disease; and improve treatment access for people with opioid use disorder.

Tuesday, September 03, 2019

Protecting Against Fungal-caused Meningitis—The fungus Cryptococcus neoformans causes a devastating form of meningitis, Cryptococcal meningitis (CM), that primarily affects patients with HIV, which suppresses patients’ immune systems. Use of anti-retroviral (ARV) therapy in the U.S. has reduced the risk that HIV-infected patients will develop CM. But CM continues to devastate patients where ARVs are not available and survival of patients with CM is only six months. Currently, there is no way to predict which HIV-infected patients will develop CM. The National Institute of Allergy and Infectious Diseases has awarded a five-year, $3.1 million grant to Liise-anne Pirofski, M.D., to look for links between natural antibodies, B-cell responses to C. neoformans, and resistance to CM and develop a risk profile to identify patients most likely to develop CM. The findings could lead to better ways to diagnose and treat CM. Dr. Pirofski is professor of medicine and of microbiology & immunology, chief of infectious diseases at Einstein and Montefiore, and holds the Selma and Dr. Jacques Mitrani Chair in Biomedical Research. (1R01AI143453)

Friday, August 30, 2019

Targeting Calcium Channels in Heart Failure—Cardiovascular disease along with subsequent heart failure is the leading cause of morbidity and mortality in the United States. The adult heart is composed of diverse cell types, including cardiomyocytes, fibroblasts, endothelial and perivascular cells, which participate in repair processes. After a heart attack, the complex interactions among these cells are dramatically disturbed, often leading to excessive or detrimental cardiac fibrosis—a hallmark of heart failure. Cardiomyocyte function is known to be regulated by calcium channels, but much less is known about the role of calcium in fibroblast functioning and in modulating fibrosis. The National Heart, Lung, and Blood Institute has awarded Gaetano Santulli, M.D., Ph.D., a five-year, $2 million grant to study the roles played by calcium channels in regulating cardiac fibrosis. Dr. Santulli is an assistant professor of medicine and of molecular pharmacology at Einstein. (1R01HL146691-01A1)

Thursday, August 29, 2019

Unintended Risks of Opioid Tapering—The use of opioid tapering—reducing opioid doses for patients on chronic opioid therapy to decrease their risk of overdose — has increased in recent years but may lead to unintended consequences. In a new study published online on August 19 in the Journal of General Internal Medicine, Hector R. Perez, M.D., and colleagues at Montefiore found that opioid tapering may be associated with termination of care, or patients leaving a healthcare system. Using electronic medical records of more than 1,600 patients who were being treated with opioids, the investigators found that patients who were tapered off opioids were significantly more likely to terminate their care than chronic opioid users whose doses were continued. The researchers note that termination of care could lead to poor outcomes including increased risk for chronic diseases such as asthma, diabetes and HIV infection. Dr. Perez is an assistant professor of medicine at Einstein and attending physician of internal medicine at Montefiore.

Thursday, August 22, 2019

Insights Into Metastasis—Cancer stem cells generate and sustain tumors, leading to tumor recurrence and metastasis. The cell cycle inhibitor p21CIP1 (p21) is a protein that plays a well-known role in halting cellular proliferation. But in previous work, Rachel B. Hazan, Ph.D.,  and colleagues have shown that p21 also exerts pro-metastatic effects in mammary tumor models via an unknown mechanism. Their paper, which published on July 1 in Molecular Cancer Research demonstrated that p21 expression activates Wnt signaling, a key signaling pathway known to be dysregulated in many types of cancer. Knocking out p21 in the PyMT mouse model of breast cancer suppressed Wnt signaling. p21 was found to turn on Wnt signaling by increasing levels of the transcription factor TCF1 and Cyclin D1, proteins that are important activators of Wnt signaling. The findings imply that targeting p21 in combination with chemotherapy might be an effective therapy against metastasis. Dr. Hazan is professor of pathology at Einstein.

Tuesday, August 13, 2019

Preventing Injury After Ischemia—Nitric oxide delivered into the circulation dilates blood vessels, increases blood flow and limits vascular inflammation—which can help people experiencing a heart attack or ischemic stroke. But administering nitric oxide systemically to patients can trigger an undesirable drop in blood pressure. Joel Friedman, M.D., Ph.D., has developed a technology that may lower the risk. In experiments involving hamsters, he and his colleagues infused nitric-oxide-containing paramagnetic nanoparticles into the animals and then used an external magnet to draw the particles to constricted vessels. The localized magnetic field restored flow and prevented vascular injury without damaging surrounding tissues. The technology could potentially become a safe, effective and rapid therapy for patients experiencing ischemia. The findings were published online on May 27 in ACS Applied Bio Materials. Dr. Friedman is a professor of medicine and of physiology and biophysics, as well as the  Young Men’s Division Chair in Physiology emeritus at Einstein.

Friday, August 09, 2019

MS Patients, Mobility and Falls—Impaired mobility is the most obvious symptom of multiple sclerosis (MS), and falls are very common. The life expectancy of MS patients has greatly increased —yet research on mobility and falls among older MS patients is scarce. Research by Roee Holtzer, Ph.D., suggests that the integrity and proper functioning of the brain, especially the prefrontal cortex, are critical for cognitive control of mobility. He has received a five-year, $3.5 million grant from the National Institute of Neurological Disorders and Stroke to identify brain systems of mobility in older adults with MS and determine whether brain function during active walking can be used to predict falls. In a study involving 120 older adults with MS and 120 controls, Dr. Holtzer will use functional Near-Infrared Spectroscopy to measure prefrontal cortex activity and efficiency during active walking as well traditional neuroimaging methods such as MRI that assess the structural integrity of the brain. They hope their findings will identify biomarkers that can be modified to prevent falls. Dr. Holtzer is a professor in the Saul R. Korey Department of Neurology at Einstein. (1R01NS109023-01A1)

Friday, July 26, 2019

Sleep and Cognitive Decline—Disturbed sleep is common among older adults and may lead to cognitive decline and Alzheimer’s disease. Carol A. Derby, Ph.D., has received a four-year, $4 million grant from the National Institute on Aging to partner with the ongoing Einstein Aging Study to examine the association between sleep patterns and cognition in 500 older adults living in the Bronx. The grant is a collaboration with Pennsylvania State University professor Orfeu Buxton, Ph.D. Using smartphones, Einstein Aging Study participants use smartphones to take surveys and tests several times a day for two weeks a year to assess their cognition. In Dr. Derby’s project, those participants will also wear a special watch to collect daily information on sleep and wear device to measure overnight oxygen levels. The data will help reveal sleep’s short-term and long-term impact on cognition, potentially leading to strategies for preventing cognitive decline. Dr. Derby is a research professor in the Saul R. Korey Department of Neurology and in the department of epidemiology & population health and is the Louis and Gertrude Feil Faculty Scholar in Neurology at Einstein.(1R01AG062622-01)

Thursday, July 25, 2019

Preventing HIV-Caused Brian Damage—HIV can invade the brain and cause chronic neural inflammation, leading to cognitive impairment in more than half of HIV-infected people. Antiretroviral therapies don’t completely relieve inflammation or reduce central nervous system damage—and opioid abuse makes things worse. The National Institute on Drug Abuse has awarded Joan W. Berman, Ph.D., and Harris Goldstein, M.D., a five-year, $4.2 million grant to investigate the molecular mechanisms that cause HIV-related inflammation in people who abuse opioids while taking antiretroviral therapies. HIV infection and opioids appear to modulate certain brain- and blood-cell genes, enabling HIV-infected cells to enter the brain and cause neuronal damage. Discovering those genes may help in identifying drugs that maintain the blood-brain barrier’s integrity and quell HIV-caused brain inflammation. Dr. Berman is the Irving D. Karpas Chair in Medicine and the Senior Academic Advisor to the Graduate Division of Biomedical Sciences, as well as a professor of pathology and of microbiology and immunology at Einstein. Dr. Goldstein is professor of pediatrics and of microbiology & immunology, the Charles Michael Chair in Autoimmune Diseases and director of the Einstein-Rockefeller-CUNY Center for AIDS Research. (1R01DA048609-01).

Monday, July 22, 2019

Seeking the Molecular Basis of Liver Disease—Among its many functions, the liver produces proteins, lipids, clotting factor and glycogen, filters blood from the digestive tract before it reaches the rest of the body, and secretes digestion-aiding bile ducts into the intestines via bile ducts. The trafficking of molecules into and out of the liver is controlled by two distinct types of liver epithelial cells: hepatocytes and bile duct cells, both of which have polarized membranes that ensure the directional flow of molecules. Anne Muesch, Ph.D., has been awarded a three-year, $1.7 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases to determine how hepatocytes and bile-duct cells organize their polarized membranes to carry out their specific yet different functions. The findings may help reveal the molecular basis of common liver diseases. Dr. Muesch is professor of developmental and molecular biology at Einstein. (1R01DK118015-01A1)

Thursday, July 18, 2019

Insights Into Obesity and HypertensionDongsheng Cai, Ph.D., received two NIH grants to study the role of the hypothalamus in obesity and hypertension. Dr. Cai has found that sustained activation of astrocytes (cells that surround and support neurons) may contribute to the metabolic dysregulation and subsequent weight gain caused by pro-inflammatory signaling in the hypothalamus. He was awarded a four-year, $2 million grant (1R01DK121435-01) to study how hypothalamic astrocytes are altered in inflammation and how those altered astrocytes influence hypothalamic neurons to dysregulate metabolism. Evidence also indicates that inflammation–induced activation of hypothalamic astrocytes plays a role in in obesity-related hypertension (OHT), which accounts for 75% of hypertension cases but is difficult to control. The second grant (1R01HL147477-01), totaling $2.5 million over four years, sponsors Dr. Cai’s research into how the astrocyte-neuron relationship in obesity contributes to OHT. Dr. Cai is professor of molecular pharmacology at Einstein.

Wednesday, July 17, 2019