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Insights Into Metastasis

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

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

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

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

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

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 Hypertension

Insights Into Obesity and Hypertension—Dongsheng 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
 
New Drug Target for HIV-1

New Drug Target for HIV-1—Immune system proteins called chemokines mobilize at infection sites and attract pathogen-fighting immune cells to the sites. But HIV-1, the virus that causes AIDS, exploits the release of a particular chemokine—CCL2—to exit host cells so it can infect new cells and replicate further. A study by Vinayaka Prasad, Ph.D., and coworkers David O. Ajasin and Vasudev Rao, M.B.B.S., published online on June 7 in eLife, describes the novel mechanism involved. CCL2 mobilizes a protein from the host cell’s actin cytoskeleton to the cellular locations of virus budding and release.  The newly discovered mechanism is broadly applicable to the replication of numerous DNA and RNA viruses and suggests a target for drugs that could stop HIV-1 from multiplying. The many CCL2 antagonists that are currently in clinical trials for treating other diseases could be directed towards blocking the spread of HIV-1. Dr. Prasad is professor of microbiology & immunology at Einstein. Other key contributors include Einstein investigators Ganjam Kalpana, Ph.D., Anne Bresnick, Ph.D., and Andras Fiser, Ph.D.

Friday, June 28, 2019
 
How Lupus Occurs in the Brain

How Lupus Occurs in the Brain—Patients with the autoimmune disease systemic lupus erythematosus (SLE) have poor outcomes despite aggressive treatment with immuno-suppressive drugs. In a study published online on June 6 in JCI Insight, Chaim Putterman, M.D., and colleagues identified how SLE develops in the central nervous system independent of its occurrence elsewhere in the body. In research involving animal models of lupus and human lupus autopsy tissue, the scientists found that the immune system forms a tertiary lymphoid structure—which functions like a lymph node—in a deep brain structure called the choroid plexus. The newly discovered structure may be the route through which the immune system promotes CNS lupus.  The findings may lead to new therapies for CNS lupus, which currently is extremely difficult to treat. Dr. Putterman is professor of medicine and of microbiology & immunology at Einstein and chief of rheumatology at Einstein and Montefiore.

Wednesday, June 26, 2019
 
New Strategy Against Deadly Lung Cancer

New Strategy Against Deadly Lung Cancer—Better treatments are needed for small cell lung cancer (SCLC), an aggressive disease with poor prognosis (5-year survival rate less than 2%). Virtually all SCLCs have inactivating mutations in the same two genes, RB1 and TP53, but all efforts to design drugs to reactivate those genes have failed.  Liang Zhu, M.D., Ph.D., and Edward Schwartz, Ph.D., received a five-year, $2.2 million grant from the National Cancer Institute to try a new approach. Their preliminary studies have shown that SCLC cannot develop in mice when one of RB1’s downstream target proteins (Skp2) is inactivated. The researchers have also identified an inhibitor of that protein that kills human and mouse SCLC tumors. Their new studies could lead to clinical trials of a therapy that might benefit most SCLC patients. Dr. Zhu is professor of developmental & molecular biology, of ophthalmology & visual sciences and of medicine at Einstein. Dr. Schwartz is a professor of medicine and of molecular pharmacology at Einstein. (1R01CA230032-01A1)

Thursday, June 13, 2019
 
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