Research Awards and Honors: September 2017

Massachusetts General Hospital’s talented and dedicated researchers are working to push the boundaries of science and medicine every day. In this series we highlight a few individuals who have recently received awards or honors for their achievements:

Aguirre

Aaron Aguirre, MD, PhD, of the Cardiology Division and the Center for Systems Biology, has received a 2017 Physician/Scientist Development Award for “Morphology and Dynamic Functions of Pericytes in the Heart.” Aguirre’s project will use state-of-the-art microscopy techniques to better understand the role of pericytes—unique cells that line the outer walls of the smallest blood vessels in the heart. Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research along with the Center for Diversity and Inclusion.

“I am grateful for the research support provided by the MGH Physician Scientist Development Award. It will allow me to expand my current research into a new direction and to generate critical preliminary data necessary for future grant applications.”

 

Chung

David Chung, MD, PhD, attending neurointensivist in the Neurology Department, has been awarded the Timothy P. Susco Chair of Research and the Andrew David Heitman Foundation Chair of Research from The Brain Aneurysm Foundation for his work, “Impact of Spreading Depolarizations and Subarachnoid Hemorrhage on Brain Connectivity.” He is one of 14 awardees, given to those whose work is impacting a disease that affects one in 50 people in the United States, often leading to death or lifelong disability.

My immediate reaction to receiving this award was gratitude towards my mentors in the Department of Neurology at MGH: Cenk Ayata, Jonathan Rosand, Guy Rordorf, and Leigh Hochberg. Without their support, this work would not be possible. A major question in Neurocritical Care is how to prevent poor outcome after a ruptured brain aneurysm. Even when we successfully repair the aneurysm, many patients will develop a syndrome of progressive brain damage for unknown reasons. This award will enable us to examine unexplored causes of brain damage and poor outcome with the goal of improving quality of life in survivors of the disease.”

 

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Julie Levison, MD, MPhil, MPH, of the Division of General Internal Medicine, has received a CFAR ADELANTE Award from the National Institutes of Health, the Office of AIDS Research and the NIH-funded Centers for AIDS Research to support new  investigators working on HIV research in Latinos. Hispanic/Latino populations in the U.S. currently bear a disproportionate burden of the HIV/AIDS epidemic. The ADELANTE team is composed of Dr. Levison (principle investigator), Dr. Margarita Alegría, chief MGH Disparities Research Unit, and Carmen Rios, Respite Case Manager at the Barbara McGinnis House.

“The ADELANTE award is a special type of research award because it recognizes the value of community-academic collaborations in overcoming disparities in HIV outcomes in Latino populations. In this study, we will use qualitative research to solicit the needs and priorities of HIV-infected Latino migrants with substance use disorders or who report male-to-male sex and we will use that feedback to tailor and evaluate a community-based intervention we have developed for HIV-infected Latinos with inconsistent HIV primary care attendance.”

 

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Fatima Cody Stanford, MD, MPH, MPA, adult and pediatric obesity medicine physician of the MGH Weight Center, Department of Medicine-Gastroenterology and Department of Pediatrics-Endocrinology, has received a 2017 Physician-Scientist Development Award from the MGH Center for Diversity and Inclusion for “Exploring Referral Patterns and Shared Decision Making Regarding Weight Loss Surgery in Adolescents and Young Adults with Moderate to Severe Obesity.” Funding for the Physician/Scientist Development Awards is provided by the Executive Committee on Research in conjunction with the Center for Diversity and Inclusion. Stanford also has been selected to the inaugural class of Emory University Alumni Association’s “40 Under Forty,” a selected group of outstanding young alumni with impressive track records who are “go-to” leaders.

“I am delighted to be the recipient of the MGH Physician Scientist Development award in partnership with the MGH Center for Diversity and Inclusion and ECOR. I believe that we are just at the beginning of discerning issues associated with addressing obesity in the pediatric and adult populations. This award allows me to ascertain information about shared decision making in adolescents and young adults with moderate to severe obesity in which weight loss surgery might be utilized to help them achieve a healthy weight. To our knowledge, no one has investigated the use of shared decision making regarding weight loss surgery in young people. This awards allows us to do just that.”

 

Temel GreerJennifer Temel, MD, director of the Cancer Outcomes Research Program and Hostetter MGH Research Scholar, along with Joseph Greer, PhD, program director of the Center for Psychiatric Oncology & Behavioral Sciences, have received a research funding award from the Patient-Centered Outcomes Research Institute (PCORI) for their research “Comparative Effectiveness of Early Integrated Telehealth Versus In-Person Palliative Care for Patients with Advanced Lung Cancer.” The new awards were given to those whose work specifically focuses on community-based palliative care delivery. The goal of this project is to determine if telehealth is an effective, patient-centered, and accessible delivery modality for early palliative care.

“We are overjoyed to receive this research award from PCORI. By testing novel models of care using telemedicine, we hope to demonstrate that greater numbers of patients with advanced cancer and their families can access and benefit from essential palliative care services closer to the time of diagnosis.”

 

Whetstine.jpgJohnathan Whetstine, PhD, of the MGH Cancer Center and Tepper Family MGH Research Scholar, has received a Lung Cancer Discovery Award from the American Lung Association. This award supports investigators at any level of research experience focusing on novel treatments or a cure for lung cancer. His goal is to use studies about histone modifiers to provide insights into tumor heterogeneity and emerging drug resistance so that better molecular diagnostics, epigenetic therapeutic molecules, or use of novel therapeutic combinations can be achieved in cancer treatment.

“We are very excited to receive this award from the ALA.  This support allows my group to continue to expand our lung cancer research program in the area of tumor heterogeneity and drug resistance. Most importantly, these resources allow us the opportunity to explore novel regulatory pathways driving heterogeneity and copy gains of regions affiliated with resistant lung cancer, which provides insights into novel diagnostics and therapeutic opportunities in this hard-to-treat cancer.”

 

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Alik Widge, MD, PhD, director of the Translational NeuroEngineering Laboratory, Division of Neurotherapeutics, has received the 2017 One Mind/Janssen Rising Star Translational Research Award from the One Mind Institute and Janssen Research & Development, LLC. This award identifies and funds pivotal, innovative research on the causes of and cures for brain disorders. Toward boosting the recovery of patients with illnesses such as schizophrenia, major depression or obsessive-compulsive disorder, Widge proposes to identify precisely the brain circuits that govern the inflexibility of thinking common among patients with such illnesses, and to test whether neurostimulation of these circuits could improve mental flexibility.

“I was very excited about the Rising Star award, for two reasons. First, it brings much-needed seed funding to our lab for an unconventional but possibly high-yield project. We have found that electrical brain stimulation in humans can improve mental flexibility — the ability to “take the road less traveled by” and explore new behavior strategies. That ability is impaired in many mental illnesses. Our problem is that we don’t yet know how the electrical stimulation improves flexibility. The Rising Star award will let us set up animal experiments to identify the circuit basis of the effect, findings we could then translate back into humans. 

Second, this is a really important award in psychiatric research. It’s brought our lab’s other work into the spotlight, which will help those projects progress. I’m grateful both to the OneMind Institute for the award and to the MGH team that helped me get the preliminary data that made it possible.”

Could an App Ease the Stress of Managing Heart Failure?

A heart failure diagnosis can be an unsettling experience. Add in a deluge of new medication regimens and lifestyle changes to implement, and the entire episode can begin to feel very overwhelming for a heart failure patient.

A new smartphone app from Jana Care, called Heart Habits, was created in the hopes of streamlining cardiac care management. Now a team at Massachusetts General Hospital wants to test out the app with patients.

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Screen shots of the Heart Habits app (photo courtesy of Jana Care)

“Heart failure patients are pretty complex,” Nasrien Ibrahim, MD, a cardiologist at Mass General and one of the lead investigators, said in a recent interview with MobiHealthNews. “We’re always looking for ways to improve patient care, reduce morbidity and mortality, to keep these patients out of the hospital or the emergency department, and just improve their overall quality of life.”

The Heart Habits app prompts patients to track their symptoms twice a week and provides alerts if any signs or symptoms, such as shortness of breath, suggest a problem that may require medical attention.

The app also provides information on and tracks other important factors including weight. Patients are prompted to record their weight on a daily basis. The data is then translated into graph form, which the patients’ care teams—who have access to the app—can easily view and interpret. The Heart Habits app also enables two-way communication with a messaging feature that allows patients to contact their physicians.

Ibrahim and her team want to investigate how patients respond to using the app and if its use improves patient symptoms. Their initial pilot will include 24 patients randomized to either the app or the standard of care—paper documents given to patients to take home—for six weeks.

“If the pilot study works, meaning the app is user-friendly, we see improvement in scores, that the patients like it, and that their symptoms have improved, a larger study would involve biomarker testing, outcome measures such as hospital readmissions and emergency department visits, and, essentially, cost as well,” Ibrahim said.

A Snapshot of Science: Zebrafish, Steroid Replacements, and Much More

We wanted to share some recent Mass General research that has been published in high impact, top-tier journals. This is just a small snapshot of the incredible research that takes place at Mass General each day — there’s lots more to find at massgeneral.org/research/news!

Exploring the Formation of the Aorta in Zebrafish

Summary submitted by Caroline Burns, PhD, d’Arbeloff MGH Research Scholar, and Geoff Burns, PhD, both researchers in the Cardiovascular Research Center at Mass General, and co-senior authors of the study

Zebrafish
Image of the head region of a zebrafish embryo (head is to the left)

The aorta and its branches are large arteries in the human body that carry oxygen-rich blood from the heart to the rest of the circulatory system. Structural malformations of the aorta are common birth defects that even in the mildest cases require life-saving surgery at birth.  During fetal life, the aorta is built from transient blood vessels termed the pharyngeal arch arteries (PAAs). However, the mechanisms regulating formation of the PAAs remain poorly understood. This paper reports that TGFb signaling, a molecular pathway that controls cellular proliferation and differentiation in other contexts, initiates and is essential for PAA development in zebrafish. Despite this important advance, further research is needed to identify additional molecular pathways that control PAA establishment and to learn if mutations that affect TGFb signaling in humans result in similar aortic deficiencies. This information can be leveraged to develop new therapies for preventing or treating congenital malformations that involve the aorta and its branches.

Managing Consciousness with Anesthesia Drugs

Summary submitted by Patrick Purdon, PhD, from the Department of Anesthesia, Critical Care, and Pain Medicine, at Mass General, and senior author of the study

This study finds evidence that propofol, an anesthetic drug frequently used in clinical practice, disrupts activity in the parts of the brain responsible for awareness and coordination by inducing highly synchronized oscillations within and between these brain structures. The study also found that during recovery of consciousness, these synchronized oscillations dissipate in a distinct “boot-up” sequence, one that did not simply mirror loss of consciousness. This implies that recovering consciousness is not just a passive process, but an active one involving a different set of brain areas responsible for “waking up” the brain. Overall, this study advances understanding of what it means to be unconscious under anesthesia, and establishes principled neurophysiological markers to monitor and manage this state.

Impact of Genetic Disease on Metabolism and Exercise

Summary submitted by Rohit Sharma, PhD, from the Department of Molecular Biology at Mass General, and co-investigator of the study

Human metabolism is “wired” to allow us to go from rest to running by efficiently burning sugars, fats and proteins to harness their energy.  However, patients with certain genetic conditions like McArdle disease who cannot access glycogen stores or mitochondrial disease who have broken respiratory chains have symptoms that are exacerbated by exercise.  Scientists from the Mootha lab studied the exercise-induced changes that occur in hundreds of plasma metabolites in healthy individuals, patients who have McArdle disease and mitochondrial disease patients.  By comparing these disorders they shed light on the typical metabolic processes that allow us to exercise and also revealed potential disease biomarkers.

Treating Blood Vessel Inflammation Without Steroids

Summary submitted by John Stone, MD, MPH, Director of the Clinical Rheumatology in the Rheumatology Unit at Mass General, and lead author of the study

Giant cell arteritis (GCA) is the most common form of blood-vessel inflammation. Complications include blindness and aneurysm. Up to now, the only known effective treatment was a steroid called prednisone which caused many complications. Now a phase 3 clinical trial has confirmed for the first time in the history of this disease that regular treatment with a drug called tocilizumab successfully reduces the need for high-dose steroid treatment. Patients who received tocilizumab plus a prednisone taper were nearly four times more likely to achieve disease remissions compared to those who received prednisone alone. Results of the trial were the basis for the Food and Drug Administration’s approval of tocilizumab to treat GCA in May 2017.

Men’s Health at MGH: Advancements in Clinical Care and Research

“Starting as early as childhood, young men have had the notion ingrained into their minds that their manhood is more important than their overall health,” says Dicken Ko, MD, Director of Massachusetts General Hospital’s regional urology program and past director of the kidney transplant program.

Ko says that men’s health in general is an often underreported and underrepresented topic, in part due to the uncomfortable nature associated with talking about subjects such as sexual dysfunction and mental health issues.

Here are just a few ways that researchers and clinicians at Massachusetts General Hospital are helping to raise awareness of and advance the field of men’s health:

Transplant

Dr. Ko was also the urologist who led the first U.S. penis transplant along with plastic surgeon Curtis Cetrulo, MD, FACS, Director of MGH’s Vascularized Composite Allotransplantation Laboratory. Read about this surgical milestone and how it’s opening a frontier for complex transplants.

 

Fertility

Male infertility affects almost half of the 45 million couples worldwide who have trouble conceiving, but current standard methods for diagnosing male infertility can be expensive, labor-intensive and require testing in a clinical setting. Researchers at Massachusetts General Hospital and Brigham and Women’s Hospital have developed a smartphone-based semen analyzer that can be used to test for male infertility in the privacy of your own home. Learn more about the device.

 

Steroids

3 to 4 million men in America have used steroids at some point. Recent findings from Aaron Baggish, MD, Associate Director of the Massachusetts General Hospital (MGH) Cardiovascular Performance Program, show long-term use of illicit steroids can reduce the heart’s ability to pump blood throughout the body, damage the heart muscle’s ability to relax and may also cause a buildup of plaque that can lead to heart attacks. Read more about this study here.

 

Homebase project

The majority of veterans are men (as of September 2016, the VA estimates that there are 18,532,000 living male veterans and 1,861,000 female veterans). Home Base, a partnership of Mass General and the Red Sox Foundation, is the only private sector clinic in New England, and the largest private sector clinic in America, with the sole focus of helping at-risk veterans and military families. Learn more about Home Base. (photo courtesy of Home Base)

Mass General Researchers Investigate the ‘Big Eaters’ of the Immune System: #MacrophageMonday

macrophage
Macrophage in the body. Credit: Cell Press

Macrophages serve a vital function in the body’s immune system— these white blood cells are in charge of engulfing pathogens, foreign materials and dead cells.

Two new studies from Massachusetts General Hospital researchers have identified two unexpected roles that macrophages play in the body. In the heart, macrophages play a beneficial role, helping heart muscle cells maintain a steady heartbeat. When it comes to fighting cancer, however, macrophages appear to play a detrimental role by interfering with immunotherapy treatments.

Macrophages prove helpful in maintaining a steady heart beat

Researchers have known for decades that macrophages can be found in high numbers around inflamed or diseased hearts to help heal damaged tissue. However, macrophages’ function in healthy hearts has remained a mystery. A new study from Matthias Nahrendorf, MD, PhD, Director of the Mouse Imaging Program at the Center for Systems Biology at Mass General, suggests that macrophages help the heart function properly and keep its rhythm.

The research began when an MRI and an electrocardiogram of a mouse heart that was genetically engineered to lack macrophages revealed that it was beating too slowly. Comparative tests of a healthy mouse heart revealed that large quantities of macrophages could be found at the atrioventricular node, which passes electricity from the atria to the ventricles of the heart.

Cardio macrophage
Heart cells (red) and macrophages (green) in a human atrioventricular node.
Credit: Maarten Hulsmans & Matthias Nahrendorf

Nahrendorf and his team found that these congregated macrophages lend a helping hand by facilitating the conduction process — they prepare heart cells for continuous bursts of electricity by creating gap junctions to connect the cells to each other so the electrical current that regulates heartbeat can flow through smoothly.

This study is a giant step forward in understanding how the heart works and communicates with the body’s cells. Nahrendorf plans to continue investigating the relationship between macrophages and conduction in the heart to answer more unresolved questions.

When macrophages rebel

Another recent study from Mikael Pittet, PhD, of the Center for Systems Biology at Mass General, suggests that macrophages aren’t always the good guys.

Using advanced imaging techniques, Pittet and colleagues were able to see how macrophages can render cancer immunotherapy drugs inactive in the body within moments of the drugs being administered.

Cancer macrophage
A macrophage (red) removing immunotheraphy drugs (yellow) from a T-cell (blue).  
Credit: Center for Systems Biology, MGH

Immunotherapy drugs are designed to bind to T-cells in the body, another type of white blood cell that relies on chemical signals to identify and kill harmful cells in the body.

One way that tumor cells avoid detection and destruction by these T-cells is by adopting a chemical signal that tumor cells use to inhibit T cells from attacking them, essentially rendering themselves “invisible” to the immune system. Immunotherapy drugs are designed to override this process by binding to T cells at the receptors that typically receive this “all is well” signal, thus making the tumor cells vulnerable to attack.

However, as Pittet and his colleagues observed, when immunotherapy drugs were administered, macrophages would clear away the drugs from the T-cells within minutes of the treatment, essentially making the treatment ineffective. Pittet’s observation also explains why this type of promising immunotherapy hasn’t been proven widely successful (the treatment can work extremely well, but only in a minority of patients).

The good news is that Pittet also determined the chemical pathway that was driving this macrophage response, and identified potential strategies for blocking that pathway in mouse models. More research is needed to determine whether similar strategies improve the results of immune checkpoint blockade in human patients.

New Study Details the Risk of Blockages, Bleeding and Death Among Patients Who Receive Stents: Five Things to Know

Researchers wanted to better understand the long-term risk of blockages, bleeding events and death among patients who received a cardiac stent. Here are five things to know about the new study recently published in JAMA Cardiology:

  1. A stent is a small, wire mesh tube (pictured below) that can strengthen a weak artery or open a narrow or blocked artery. Patients who have received a cardiac stent are at greater risk for blockages in blood flow to the heart or brain (called ischemic events) as a result of their heart disease or from clotting inside the stent. The use of aspirin combined with other similar drugs (called dual antiplatelet therapy) to prevent these incidents in the first year after receiving a stent has become standard practice. However, while dual antiplatelet therapy decreases risk of ischemic events, it also increases risk of fatal bleeding or bleeding in vital organs (called bleeding events) when continued longer than one year.Stent
  2. This new study, led by Eric Secemsky, MD, MSc, a fellow in the Massachusetts General Hospital Division of Cardiology, looked at data from over 11,000 participants who underwent dual antiplatelet therapy for one year following the placement of a stent and had no ischemic or bleeding events. The participants were then randomized to either continue with the dual therapy for 18 months, or to receive aspirin plus placebo instead.
  3. Researchers found that taking both medications for a total of 30 months decreased ischemic risk (1.6% drop in ischemic events) while also increasing bleeding risk (0.9% increase in bleeding events). Overall, having either an ischemic or bleeding event severely increased risk of death – an 18-fold risk increase after any bleeding event and a 13-fold risk increase after any ischemic event.
  4. In a previous study, Secemsky developed a risk score that can help determine whether or not dual antiplatelet therapy should continue past the one-year mark. This tool, which is utilized by the American College of Cardiology, can help clinicians decide what treatment to prescribe. You can find it on the ACC website.
  5. With the understanding that both ischemic and bleeding events are associated with high risk of mortality, future efforts will focus on individualizing treatment and identifying patients who are likely to experience more benefit than harm from dual therapy.

Eric Secemsky, MD, MSc, a fellow in the Massachusetts General Hospital Division of Cardiology, is lead author on this study. Click here to learn more.

Mass General Scientists are Growing New Hearts in the Cells of Old Ones

(From an article in Atlas Obscura by Sarah Laskow)

For decades now, there’s been an image of human regeneration being a few cells dividing in a petri dish, hopefully growing into a shiny new organ. But the truth is that scientists’ work is a bit more macabre. To make a new organ, it helps to be working from a dead one.

That goes for hearts, too. A little more than a decade ago, Dr. Harald Ott, now a surgeon at Massachusetts General Hospital and a professor at Harvard Medical School, developed a procedure that could rinse an organ of its cells, leaving behind an empty structure that can be repopulated with new ones. In the lab, Ott and his colleagues have taken ghostly hearts and resurrected them as new ones. Shocked with electrical pulses, those new hearts have even started beating again.

READ THE ARTICLE