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Using Ultrasound to Treat Cancer

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

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

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

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

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

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

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

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

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

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
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