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.

Using Ultrasound to Treat Cancer—Tumors evade the immune system by inducing T cell tolerance, a state where T cells don’t recognize tumors as foreign and therefore don’t attack them. Thus, a major challenge for cancer immunotherapy is overcoming T cell tolerance. The National Cancer Institute awarded Fernando Macian-Juan, M.D., Ph.D., and Chandan Guha, M.B.B.S., Ph.D., a five-year, $1.9 million grant to study low-intensity focused ultrasound (LOFU) as a way to activate the immune system to combat tumors.  In previous work involving melanoma, the researchers found that LOFU reverses T cell tolerance and activates anti-tumor T cell responses. The team will test LOFU in a mouse model of melanoma to better understand how LOFU works and to test its effectiveness and safety when combined with immunotherapies. Dr. Macian-Juan is professor of pathology at Einstein. Dr. Guha is professor and vice chair of radiation oncology at Einstein and Montefiore Health System. Dr. Guha is also professor of urology and of pathology at Einstein and is director of Einstein’s Institute for Onco-physics. (1R01CA226861-01)

Monday, June 04, 2018

Making Vaccines More Effective—After vaccination or infection, antibody-secreting cells (ASCs) are responsible for maintaining antibody production. Most useful of all are long-lived ASCs, which are found in the bone marrow and churn out antibodies over a person’s lifetime. One way to bolster ASCs’ antibody output would be to increase the number of long-lived ASCs. The NIH has awarded David Fooksman, Ph.D., a five-year, $2 million grant to find ways of increasing levels of long-lived ASCs following Dr. Fooksman and colleagues have shown that cell membranes of long-lasting ASCs express high levels of a proteoglycan called CD138. They believe that those high levels of CD138 give long-lasting ASCs a survival advantage over new ASCs, and they will use the NIH grant to test that theory. The researchers will also explore ways of increasing CD138 levels as a way to enhance the survival of long-lasting ASCs and improve long-term immunity. Dr. Fooksman is an assistant professor of pathology and of microbiology & immunology at Einstein. (1R01HL141491-01)

Thursday, May 31, 2018

How a Motor Protein Breaks its Tracks—Kinesins are motor proteins found in eukaryotic cells that walk along microtubules. Members of a subfamily of kinesins, the kinesin-13s, do something different: they shorten microtubules to reshape the cytoskeleton during mitosis and other cellular processes. To identify the mechanism behind this atypical kinesin activity, Hernando Sosa, Ph.D., and his colleagues Mathieu Benoit and Ana Asenjo used cryo-electron microscopy to determine the structure of kinesin-13s bound to microtubules. The findings, published online on April 25 in Nature Communications, reveal for the first time how kinesin 13s are adapted to shorten microtubules rather than walking along them. The findings also suggest targets for modulating kinesin activity and microtubule dynamics that could lead to new anti-cancer drugs. Dr. Sosa is an associate professor of physiology & biophysics at Einstein.

Tuesday, May 29, 2018

Near-Infrared Biosensor for Multiplex Imaging—A family of enzymes called GTPases regulates cell organization and movement and controls the development of cancer and autoimmune diseases. Visualizing how GTPases function can provide insights into how they influence health and disease. In a study published online on April 23 in Nature Chemical Biology, Louis Hodgson, Ph.D., and Vladislav Verkhusha, Ph.D., engineered a new monomeric near-infrared fluorescent protein that absorbs and emits light in the region of the electromagnetic spectrum in which light can pass through animal tissues. By attaching the near-infrared fluorescent protein to a biological sensing domain that detects GTPase activities, the researchers have engineered the first near-infrared biosensor. The biosensor allowed researchers for the first time to simultaneously visualize multiple GTPase activities using near-infrared light and perform optogenetic activation of GTPases in single cells, providing an unprecedented view of cellular processes. Biosensors based on the near-infrared fluorescent protein could also allow for deep-tissue imaging in living animals. Dr. Hodgson is an associate professor, and Dr. Verkhusha is a professor, both of anatomy and structural biology and the Gruss Lipper Biophotonics Center at Einstein.

Thursday, May 24, 2018

Training Addresses Patients' Social Needs—Physicians can play an important role in addressing social conditions in which patients live and that influence their health—so-called social determinants of heath (SDH). In a pilot study, Lauren Shapiro, M.D., Darlene LeFrancois, M.D., and colleagues showed that a novel curricular intervention can help medical residents identify SDH in an outpatient setting and reduce the need for social work referrals. Thirty-eight internal medicine residents at two Montefiore outpatient clinics participated in a curriculum focused on recognizing SDH via triggers such as missed medical visits and uncontrolled chronic diseases. Compared to a control group that did not receive training, the trained residents submitted 47 percent fewer social work referrals over the 16-month study. The results, published online on April 13 in the Journal of General Internal Medicine, suggest that similar programs could lead to better recognition of social determinants of health. Dr. Shapiro is an assistant professor of medicine at Einstein and director of the Einstein Montefiore Internal Medicine Residency Program. Dr. Darlene LeFrancios is associate professor of medicine and director of medical education for the Einstein Montefiore Internal Medicine Residency Program.

Tuesday, May 22, 2018

A New AML Treatment Target—The blood cancer acute myeloid leukemia (AML) is driven by leukemic stem cells (LSCs) that develop abnormally and proliferate excessively, until they ultimately displace healthy blood stem cells from the bone marrow. LSCs typically resist chemotherapy, so better strategies are needed to eliminate them. In a study published online on May 17 in the Journal of Experimental Medicine, researchers led by Ulrich Steidl, M.D., Ph.D., describe a promising target: a signaling protein called interleukin-1 receptor accessory protein (IL1RAP), which is often highly expressed on the surface of leukemic stem cells but is largely absent from normal blood stem cells. IL1RAP turned out to be crucial for leukemic stem cell survival. When AML cells (including leukemic stem cells) were isolated from patients, the researchers found they could kill those cells by targeting IL1RAP using techniques including anti-IL1RAP antibodies and gene deletion. Unexpectedly, the researchers found that IL1RAP has a much broader function in AML cells than previously realized: the protein, simultaneously stimulated multiple leukemia-promoting molecules, which makes therapeutically targeting IL1RAP particularly attractive. Dr. Steidl is the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research, director of the Stem Cell Isolation and Xenotransplantation Facility and a professor of cell biology and of medicine at Einstein and associate chair for translational research in oncology at Montefiore.

Thursday, May 17, 2018

Functional Liver Grown in Placenta—In the first use of human placenta for tissue engineering, Sanjeev Gupta, M.D., M.B.B.S., and colleagues seeded scaffold-supported human placentas with liver fragments from sheep, and the fragments developed into viable liver tissue. The achievement offers a new way to overcome donor liver shortages and help people awaiting liver transplants. The liver fragments that were transferred to the placentas contained all the cell types that comprise livers. The fragments grew within the placenta to form liver tissue with the same structure and functional ability (e.g., maintenance of albumin and urea synthesis) as the actual organ. When grafts of this liver tissue were transplanted into a sheep with liver failure, they rescued the sheep from liver failure and helped regenerate the damaged organ. The study was published online on March 26 in Hepatology. Dr. Gupta is professor of medicine and of pathology and is the Eleazar & Feige Reicher Chair in Translational Medicine at Einstein and is an attending physician at Montefiore Health System.

Tuesday, May 15, 2018

Reviving Old Blood-Making Cells—White cells, red cells and all other blood cells in the body are produced by hematopoietic (blood-forming) stem cells (HSCs) in bone marrow niches. Over time, HSCs age and produce fewer cells, which can lead to blood disorders and weakened immunity. In a study published online on May 7 in Nature Medicine, Paul Frenette, M.D., compared bone marrow from young and old mice. He found that age-related loss of sympathetic nerve signaling causes remodeling of blood vessels in the bone marrow, leading to aging of the marrow. Dr. Frenette and his team showed that stimulating old bone marrow with sympathetic nerve signaling reverses HSC aging by rejuvenating the niche. The findings could lead to new treatments for HSC-related blood disorders. Dr. Frenette is professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein.

Monday, May 07, 2018

Treating Radiation Exposure—Exposure to high-dose radiation from nuclear accidents or terrorism can cause acute radiation syndrome (ARS)—illness due to the death of stem cells in specific tissues. The main cause of death from ARS—destruction of bone marrow—can be prevented with a bone marrow transplant. But survival is extremely unlikely when radiation exposure is high enough to damage the gastrointestinal tract. Chandan Guha M.B.B.S., Ph.D., has shown that ARS of the gastrointestinal tract can be treated with a bone marrow adherent stromal cell transplant (BMASCT), which consists mainly of stromal (connective tissue) and myeloid (bone marrow) cells. The National Institute of Allergy and Infectious Diseases has now awarded Dr. Guha a five-year, $2.7 million grant to develop strategies for applying BMASCT therapy in a mass-casualty situation. Dr. Guha is professor and vice chair of radiation oncology at Einstein and Montefiore Health System. Dr. Guha is also professor of urology and of pathology at Einstein and is director of Einstein’s Institute for Onco-physics. (1U01AI138324-01)

Wednesday, May 02, 2018

Studying the Dynamics of Cell Growth—Dysregulated cell growth leads to cancer and many other diseases. In many cases, a mutation to the p53 tumor suppressor gene triggers aberrant cell growth. The National Institute of General Medical Sciences has awarded Robert Coleman, Ph.D., a four-year, $1.3 million grant to study the interplay between p53, chromatin (the complex of DNA and protein that forms chromosomes) and transcriptional bursting in single cells (when transcription from DNA to RNA occurs in bursts or pulses). Dr. Coleman and colleagues will use a single molecule live cell imaging system to directly visualize the p53 protein and the molecules it recruits to tightly regulate DNA repair, DNA replication and cell division. Insights into how this system is coordinated may lead to therapies to restore normal cellular growth in cancer and other diseases. Dr. Coleman is an assistant professor of anatomy and structural biology. (1R01GM126045-01A1)

Monday, April 30, 2018

Fat and Fit is a Myth—Many studies over the past 20 years have found that a relatively low, or “normal,” body mass index (BMI) is associated with the lowest risk of dying. But other studies suggest a possible “obesity paradox”: a survival benefit for people who are overweight or even obese. In the first study to systematically examine how muscle mass might affect the BMI-mortality relationship, Einstein researchers, led by Matthew Abramowitz, M.D., analyzed the body composition of 11,687 participants in the National Health and Nutrition Examination Survey. In results published online on April 11 in PLOS ONE, they found that muscle mass—which is inversely associated with the risk of death—influences the association between BMI and mortality risk. When muscle mass is taken into account, any apparent survival advantage to being overweight or obese disappears, along with the obesity paradox— emphasizing the importance of weight loss and other anti-obesity interventions, even for people whose BMIs are only moderately elevated. Dr. Abramowitz is associate professor of medicine at Einstein and attending physician at Montefiore Health System.

Wednesday, April 25, 2018

Unlocking Food Craving—The nucleus accumbens (NAc), a part of the brain associated with motivation and reward, may hold a key to understanding why people crave high-calorie foods. In a study published online on March 27 in eLife, Saleem M. Nicola, Ph.D., and his graduate student Kevin Caref found that the NAc’s naturally occurring opioids and opioid receptors activate neurons, which then promote the desire to eat palatable foods after animals reach satiety. In a series of trials, Dr. Nicola trained satiated and non-satiated rats to respond to cues indicating they’re about to receive high-fat food. He observed that the opioid system enhanced neuronal activity—and the desire to eat fatty foods—only in rats that were not hungry. The findings suggest that drugs that block the opioid receptors from stimulating neurons could potentially treat obesity. Dr. Nicola is an associate professor in the Dominick P. Purpura Department of Neuroscience and of psychiatry and behavioral sciences at Einstein.

Monday, April 23, 2018

Early Programming of Childhood Obesity—More than one-third of U.S. children are classified as overweight or obese. Studies show that children born underweight are at higher risks for obesity, cardiovascular disease, and type 2 diabetes. Researchers believe that one cause of obesity involves changes in the nongenetic (i.e., epigenetic) influences on gene expression—in particular, changes in the pattern of DNA methylation. The Eunice Kennedy Shriver National Institute of Child Health & Human Development has awarded Maureen Charron, Ph.D., and Mamta Fuloria, M.B.B.S., a five-year, $3.4 million grant to study DNA methylation of blood cells of intrauterine growth restricted infants, who are at high risk for becoming obese. More specifically, Drs. Charron and Fuloria will examine the children’s blood at birth and at age two to determine how DNA methylation has affected their CD3+ T-cells--immune cells that plays a key role in the development of obesity. Dr. Charron is professor of biochemistry, of medicine, and of obstetrics & gynecology and women's health at Einstein. Dr. Fuloria is an associate professor of pediatrics at Einstein. (1R01HD092533-01A1)

Friday, April 20, 2018

New Approaches Against Zika Infection—The number of mosquito-borne Zika virus infections in humans are expected to increase, and drugs for protecting people are urgently needed.  In a study published online on March 23 in Virology, Felipe Diaz-Griffero, Ph.D., describes a family of therapeutic agents that halts the virus’ entry into cells. Theorizing that Zika requires a cellular protein called AXL to attach to cells, Dr. Diaz-Griffero found that cells in which the gene for AXL was deleted were resistant to infection. The drugs may also thwart Zika infection through a second mechanism: by neutralizing acidic compartments within the cells. This group of drugs could potentially treat people infected with Zika and thereby help prevent the well-established neurological problems associated with Zika. Dr. Diaz-Griffero is professor of microbiology & immunology and the Elsie Wachtel Faculty Scholar at Einstein.

Wednesday, April 18, 2018

Boosting T Cells’ Attack—Cell-membrane molecules called glycolipids help cells recognize one another and play an important part in launching immune responses. One class of glycolipids, called alpha-galactosylceramides, have been used as a drug to activate a portion of the immune system’s T cells and effectively treat cancers in laboratory mice, although so far this has been difficult to achieve in people with cancer. Steven Porcelli, M.D. and colleagues have found that simultaneously making two different chemical changes to the structure of alpha-galactosylceramides renders them more effective at stimulating T cells to attack cancers, especially in experiments that more accurately replicate cancer in humans. Their approach, described online on March 22 in Cell Chemical Biology, is a step toward improving current drugs and creating new immunotherapies for cancer. Dr. Porcelli is professor and chair of microbiology & immunology, professor of medicine and the Murray and Evelyn Weinstock Chair in Microbiology and Immunology at Einstein.

Monday, April 16, 2018

Preventing Diabetes in Men—Men of color in low-income urban neighborhoods face a high risk for developing type 2 diabetes but are less likely to participate in diabetes prevention programs. To better engage them, Elizabeth Walker, Ph.D., R.N., and colleagues launched the first NIH-funded pilot study of a modified diabetes prevention program tailored to these men with prediabetes. In the 16-week “Power Up for Health” program, based on the National Diabetes Prevention Program, 29 middle-aged men agreed to attend weekly sessions with male lifestyle coaches at five New York City recreation centers. The coaches offered the men support, guidance and motivation for choosing healthier diets and increasing exercise, and researchers monitored their weight loss, lifestyle activities and signs of depression. The findings--published online on March 15 in the American Journal of Men’s Health, alongwith two additional reports (report 1 and report 2) of analyses of the program’s design and participants’ feedback--showed that the 23 men who completed the program lost an average of 9.7 pounds and saw improvements in depressive symptoms, diet and exercise. Dr. Walker and colleagues concluded that “Power Up for Health” shows promise for delaying or preventing type 2 diabetes among men at risk for the disease and that further research is needed with a larger sample size of men. Dr. Walker is professor of medicine and of epidemiology & population health, and is director for the pilot and feasibility program of the New York Regional Center for Diabetes Translation Research (CDTR) at Einstein.

Friday, April 13, 2018

Turning Back the Clock—Aging is usually accompanied by cellular and organ deterioration, due in part to key cellular maintenance pathways that no longer work properly. One such pathway is chaperone-mediate autophagy (CMA), responsible for selectively degrading used proteins so they don’t impair cell function. Ana Maria Cuervo, M.D., Ph.D., has received a five-year, $2.2 million NIH grant to study CMA activity in different organs to better understand why CMA efficiency degradation tails off in elderly people. Interventions that could rev up CMA could potentially slow down the aging process and delay the onset of age-related problems such as neurodegeneration, metabolic disorders and muscle weakness. Dr. Cuervo is professor of developmental and molecular biology, of anatomy and structural biology, and of medicine. She is co-director of the Institute for Aging Research and holds the Robert and Renée Belfer Chair for the Study of Neurodegenerative Diseases at Einstein. (4R37AG021904-17)

Thursday, April 12, 2018

Insights Into Antibody Creation and Cancer—The immune system relies on mutations in genes that code for antibodies to produce the wide variety of antibodies that protect us against pathogens. The enzyme causing these mutations, activation-induced deaminase (AID), sometimes mutates other genes as well, leading to B-cell lymphoma and other cancers. Matthew Scharff, M.D., and Thomas MacCarthy, Ph.D., from Stony Brook University, were awarded a five-year, $2.9 million National Institute of Allergy and Infectious Diseases Multiple Principle Investigator grant to determine how AID targets specific regions within antibody genes. Using computational modeling of antibody gene sequences and biological experiments, the team will identify DNA signatures within antibody-coding genes that attract AID activity. Learning more about the mechanisms underlying antibody diversification could lead to strategies for producing protective antibodies in patients. In addition, understanding how AID induces gene mutations could help to identify factors that put people at risk for cancer. Dr. Scharff is a distinguished professor of cell biology and of medicine and holds the Harry Eagle Chair in Cancer Research/National Women’s Division. Dr. MacCarthy is assistant professor of applied mathematics and statistics at Stony Brook University, who did his postdoctoral training with Dr. Aviv Bergman at Einstein. (1R01AI132507-01A1)

Monday, March 26, 2018

Strategies to Tackle the Opioid Epidemic—Widespread use and misuse of prescription opioids has led to a nationwide opioid epidemic. Better public health policies and strategies are needed to address the crisis. Joanna Starrels, M.D., M.S., treats and studies both chronic pain and addiction. Dr. Starrels has received a five-year, $943,000 NIH grant to mentor junior investigators to conduct research that will improve patient care and public policy approaches to curb the opioid epidemic. For example, she will study how best to reduce opioid doses for patients with chronic pain who are treated in primary care or HIV treatment settings. Dr. Starrels is associate professor of medicine and attending physician at Montefiore Health System. (1K24DA046309-01)

Thursday, March 22, 2018

Mechanisms in Diabetic Bone Loss —Diabetes affects the way sensory fibers in bones receive mechanical and neural signals. That means bone mass doesn’t increase as it normally does in response to mechanical stimulation. With a five-year, $2.1 million grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Mia M. Thi, Ph.D., and Sylvia O. Suadicani, Ph.D.,  will build on previous research suggesting that the protein complex Panx1-P2X7R influences bones’ ability to receive and respond to signals. They will examine whether diabetes affects the bones’ sensory fibers; if regulating Panx1-P2X7R is essential for bone adaptation; and if dysfunction of this protein complex triggers inflammation that impairs bone growth. Using animal models of type 1 diabetes, they will investigate new treatments for stemming diabetic bone loss. Dr. Thi is an assistant professor of orthopaedic surgery and an instructor in the Dominick P. Purpura Department of Neuroscience. Dr. Suadicani is associate professor of urology and is an assistant professor in the Dominick P. Purpura Department of Neuroscience. (1R01AR073475-01)

Tuesday, March 20, 2018