Meet a Mass General Postdoc: Robert Lochhead

This week is National Postdoc Appreciation Week, a time to recognize the significant contributions that postdoctoral scholars make to the research community.

In celebration, all this week we’ll be sharing profiles of just a few of the amazing postdocs here at Mass General to highlight their research and what inspires them.

First, we’d like to introduce Robert Lochhead, a clinical research fellow for the Center for Immunology and Inflammatory Diseases in the Division of Rheumatology, Allergy & Immunology:

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Where did you get your PhD from?

I got my PhD in microbiology and immunology from the University of Utah School of Medicine.

What questions are you asking in your current research?

I am studying the immunopathology of Lyme arthritis, and the relationship between infection and autoimmunity.

What do you hope to find out?

From a microbial and immunological perspective, Lyme disease is a fascinating human infectious disease model. The pathogen, Borrelia burgdorferi, is highly adapted to hiding from the immune system within connective tissue, resulting in infections that can go undetected for many months. What’s more, there is a wide range of disease manifestations and severity, depending on both host and pathogen factors. Lyme arthritis, the most common late-disease manifestation, may persist or worsen even after the bacteria have been cleared by antibiotic therapy, called post-infectious Lyme arthritis. My research is focusing on how B. burgdorferi infection and subsequent tissue damage may trigger chronic autoimmune arthritis, with the hope of determining mechanisms of how infection may induce autoimmunity.

What drew you to this field?

As a young graduate student interested in host-pathogen interactions, I was attracted to the immunology of Lyme arthritis as a model of studying infection-induced autoimmunity. I’ve stuck with Lyme disease ever since, first in mouse models as a graduate student, now in humans as a postdoc.

What is a typical day like for you?

I spend most of my time analyzing big RNA sequencing datasets, in the microscope room, collecting and processing clinical samples, and writing grant applications and manuscripts. Right now my typical day is mostly writing.

What do you like most about being a postdoc at MGH?

Without a doubt, the best thing about being a postdoc here at MGH is the opportunity to collaborate with wonderful clinicians and patients who are so invested in the research side of human disease. Seeing the impact of these diseases on patients brings an urgency and focus to my research that will certainly shape the rest of my scientific career.

Researchers and Clinicians Revolutionize Prevention Efforts for Brain Disease

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What if you had a strong family history of Alzheimer’s disease, but weren’t currently showing any symptoms? What could you do to stave off the cognitive decline and loss of memory associated with this devastating disease? A team of researchers and clinicians at Massachusetts General Hospital wants to be your resource in situations like these.

The Institute for Brain Health at Mass General is revolutionizing the way we treat brain disease by developing new strategies for prevention, risk reduction and early treatment. They work with individuals who are at high genetic risk for brain diseases as well as healthy individuals who want to maintain good brain function as they age.

The Institute encourages life-long relationships with its patients to support the establishment of healthy brain habits and to provide guidance when new illnesses develop that can impact the brain. In doing so, the research team is able to collect longitudinal data about the development and progression of brain diseases throughout the life cycle. This data is helping to advance understanding about the progression of diseases like Alzheimer’s, in which so much is still unknown.

Learn more about the Institute for Brain Health in this article.

The Research Institute:
Saving Lives Through Science
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The Massachusetts General Hospital Research Institute is the largest hospital-based research program in the United States, with a community of over 10,000 people working across more than 30 institutes, centers and departments.

Our researchers work side-by-side with physicians to pioneer the latest scientific advancements for curing disease and healing patients in Boston, across the United States and around the world.

To learn more about the Research Institute, please visit our website.

Obesity Prevention Researchers Make Strides with First 1,000 Days Program

How early should we start taking steps to prevent childhood obesity? It could be before the baby is even born.

That’s the thinking of the research team behind the First 1,000 Days Program, an initiative launched by Massachusetts General Hospital for Children that provides assistance to women during the timeframe believed to be most critical to their child’s health – pregnancy and the first two years after birth.

The program is led by Elsie Taveras, MD, MPH, chief of General Pediatrics at MGHfC, and Derrie Shatsel, MD, MPH, executive director of The Kraft Center for Community Health at Partners HealthCare.

Here are some quick facts about the growing childhood obesity problem in the United States:

  • One in 10 infants are considered overweight
  • By kindergarten, an estimated 1 in 5 children are overweight or obese
  • Being overweight or obese increases the risk of developing diabetes, high blood pressure and early heart disease
  • Overweight or obese children are also at an increased risk of being bullied, which can cause additional psychological problems

The 1,000 Days Program is based at the MGH Health Centers in Chelsea and Revere, and is designed to provide expectant mothers with the tools and resources needed to get their children off to a healthy start in life.

The research team is working to address childhood obesity by:

  • Encouraging pregnant women to maintain a healthy weight throughout pregnancy
  • Working with parents to help them distinguish between different cries from their children, so they don’t mistakenly feed a sleepy child
  • Advocating the complete elimination of juice and sugary drinks, which contribute to weight gain and cavities
  • Encouraging breastfeeding if possible, and if bottle feeding, for parents to watch for cues that the baby is full in order to prevent overfeeding
  • Holding off on introducing solid foods until at least four months, six months if possible
  • Revising expectations so toddlers are not required to clear their plate at every meal

The team also encourages parents to set a good example for their children by eating healthy as well.

The goal of the program is to reach 1,000 women during 2017. As of April the team had already met with over 600 women.

A portion of the study is supported by Dr. Taveras’ MGH Research Scholar award. These philanthropy funded awards provide investigators at Mass General with unrestricted funds that they can use to pursue promising new avenues of research. Taveras is an Ofer and Shelly Nemirovsky MGH Research Scholar.

Read more about the 1,000 Days Program here.

A Snapshot of Science: Detection of Alzheimer’s Disease, Development of Type 1 Diabetes, 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!

 

DETECTING AND TREATING STIFF TUMORS
Published in Nature Scientific Reports on August 14, 2017
(Summary submitted by Peter Caravan, PhD, of the Martinos Center for Biomedical Imaging)

In tumors, cancer cells are surrounded by a collection of proteins, enzymes, sugars, lipids, and minerals called the extracellular matrix (ECM). Many cancers have a fibrotic ECM, making the tumor stiff and preventing delivery of anti-cancer drugs. The presence of a fibrotic ECM is often associated with poor prognosis. We developed a new MRI method to detect tumor fibrosis non-invasively, and studied its effect in a mouse model of pancreatic cancer. The potential impact of this work is a new tool to stage the aggressiveness of tumors, guide treatment planning, and monitor the effectiveness of new tumor ECM altering treatments.

 

IMPACT OF BLOOD AND URINE FILTRATION IN LEAKY KIDNEY FILTERS
Published in Scientific Reports on August 16, 2017
(Summary submitted by Hua A. Jenny Lu, MD, PhD, of the Nephrology Division)

One major function of the kidney is filtering blood through an intricate “glomerular filter”. Disruption of any components of this highly sophisticated and dynamic filter’s structure leads to proteinuria (protein in the urine), a condition frequently seen in diabetic nephropathy and many other glomerular diseases. How blood filters though the glomerular filter and how proteinuria develops when the filter becomes leaky has not been well understood. This paper reports the application of a novel and powerful scanning microscopy technology, the Helium Ion microscopy (HIM) to identify previously unrecognized ultrastructural abnormalities of proteinuric glomerulopathy in animals. These newly discovered abnormalities provide important insight into the molecular and cellular mechanism underlying proteinuria kidney diseases.

 

OBSERVING THE DEVELOPMENT OF TYPE 1 DIABETES
Published in PNAS on August 24, 2017
(Summary submitted by Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology)

Type 1 diabetes (T1D) is an autoimmune disease where insulin-producing cells are destroyed. Inflammation in islets of human patients has been hard to evaluate, given the challenging access to material. Now, our research team has discovered how the different cellular players interact. We created new reporter mice and new imaging agents where cells of interest (lymphocytes, macrophages, dendritic cells, beta cells) are fluorescent and can be observed by imaging. We were able to observe the intricate “dance” of different immune cells interacting with each other as diabetes develops. Throughout the process, Tregs (a unique type of T-lymphocyte) control the activation of many cell types. The “dynamic geography” of events uncovered here provide important clues to immunoregulation that underlies diabetes development.

 

NON-INVASIVE MEASUREMENT OF BRAIN ACTIVITY AND MEMORY ENCODING
Published in Scientific Reports on August 25, 2017
(Summary submitted by Meryem Yucel, PhD, of the Martinos Center for Biomedical Imaging)

Alzheimer’s disease (AD) is the most frequent cause of severe memory loss in the elderly. Early detection of AD is the key to preventing, slowing or stopping the disease. Near-infrared spectroscopy (NIRS) is a non-invasive neuroimaging technique capable of monitoring brain activation. Here, we investigated the utility of fNIRS in measuring the brain activity of healthy adults during memory encoding and retrieval under a face-name paired-associate learning task. Their study demonstrates that fNIRS can robustly measure memory encoding and retrieval-related brain activity. Future work will include similar measurements in populations with progressing memory deficits. Their approach, if successful, will introduce a non-invasive, inexpensive and easily accessible tool for identifying early stages of AD.

Hackathon Revolutionizes Care with Plan to Reduce Deadly Opiate Overdoses

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Members of We Are Allies, from left, Jessica Moreno, PharmD, Kristian Olson, MD, and Benjamin Bearnot, MD

When it comes to stopping the deadly effects of an opiate overdose, time is of the essence. Every moment that the brain is deprived of oxygen increases the risk of permanent damage or death. Overdoses can be reversed by administering a drug called Narcan, but the treatment has to be delivered quickly. A team of clinical specialists at Massachusetts General Hospital is hoping to revolutionize the way we respond to overdoses by putting Narcan in the hands of team of citizen volunteers who are ready to help whenever—and wherever—an overdose happens.

The Opioid Epidemic

There were 1,531 confirmed deaths attributed to opioid overdoses in Massachusetts in 2015, according to statistics recently released by the state. With the opioid epidemic continuing to spiral out of control nationwide, there’s a need to find a solution to curb the staggering number of deaths by overdose.

Help could be on the way thanks to an innovative new concept that emerged from a Fall 2016 hackathon put on by the Center for Affordable Medical Technologies (CAMTech) and Global Medicine at Mass General and sponsored by the GE Foundation.

The Allies Concept

The three-day hackathon provided an opportunity for three Mass General specialists—Kristian Olson, MD, the Medical Director of CAMTech and a core educator in the Department of Medicine, Benjamin Bearnot, MD, a primary care physician and Innovation Fellow at MGH Charlestown, and Jessica Moreno, PharmD, a clinical pharmacist at Mass General—to collaborate on a plan for reversing overdoses before they do lasting damage.

Olson, Bearnot and Moreno were part of a nine-person team that also featured an industrial designer, an engineer, an industry pharmacologist, and importantly, people in recovery.

Their plan, titled We Are Allies, calls for equipping everyday citizen volunteers with an easy to administer spray version of anti-overdose drug naloxone, commonly known by the brand name Narcan®.

Overdoses can be deadly because opiates bind to receptors in the brain and spinal cord that are responsible for keeping us breathing. When an overdose occurs, these receptors can slow down or stop working all together, which means the body can essentially “forget” to keep breathing. Naloxone reverses the effects of an overdose by releasing the hold that opiates have on the receptors.

It does not have an adverse affect on someone who is not having an opioid overdose, which makes it safe to administer if an overdose is suspected but not confirmed.

The team believes that getting naloxone into the hands of more people will increase the odds that someone will be nearby to help when an overdose occurs. Naloxone is relatively easy to get and safe to use, but many people—even doctors—don’t carry it with them on a regular basis.

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The Allies’ distinctive purple carrying case is designed to let others know that the person is carrying the anti-overdose drug naloxone

Another key component of the team’s plan is to have the Allies carry their naloxone in a bright purple pouch that can be attached to their handbag or workbag. This distinctive design will let others know that the person is carrying naloxone and is ready to help if needed.

“Not enough people have easy access to this life-saving medication, especially in situations where it is needed most,” says Moreno. “On top of that, those who do need it may be afraid or ashamed to seek it out due to the stigma they face every day. We hope to address both of these issues head-on by encouraging Allies to essentially wear the naloxone on their sleeves in our carrying cases.”

Reducing Stigma

The team hopes the high visibility purple pouches and indicator pins will also raise the public profile of the Allies in the community, which may help to foster new conversations about opioid use disorder and reduce the stigma and sense of isolation that many who suffer from the disorder experience.

“We thought that ‘ally’ was such a great term,” explained Olson. “We rallied around it because it changed the notion of isolation. We wanted to say; ‘We’re all allies in fighting opioid use disorder.’”

For more details on the program including training videos and information on how to sign up as an ally, please visit http://www.becomeanally.com/.

More than Just Hindering Fires – Can Flame Retardants Interfere with Fertility?

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In a new study published in Environmental Health Perspectives, a team of researchers investigated the potential connection between exposure to flame retardant chemicals found in household products— called PFRs — and pregnancy. While we can’t conclude from the results that products like yoga mats cause infertility, the findings bolster pre-existing research suggesting an association between PFRs and reproductive complications.

What are PFRs?
PFRs (organophosphate flame retardants) are a class of chemicals that are commonly used in the polyurethane foam in upholstered furniture, baby products such as nursing pillows, bouncers, and swings, and yoga mats (to name a few) to make them less flammable.

What’s the risk with PFRs?
They can spread from the foam into the air and dust. Considering the ubiquity of PFR-containing products, we likely inhale the chemicals on a regular basis without even knowing it. Although scientists don’t yet have enough conclusive evidence to say that PFRs are bad for our overall health, a growing body of research suggests exposure to PFRs can disrupt the hormones involved in reproduction and embryo/fetus growth. This new study expanded the evidence base by specifically looking at possible connections between exposure to PFRs and pregnancy.

What did the study involve and what did they find?
A team of researchers, including Mass General’s Russ Hauser, MD, MPH, ScD, followed 211 women who went to the Mass General Fertility Center to be evaluated for in vitro fertilization (IVF). The researchers checked the women’s urine for traces of PFRs and found that more than 80% of the women had traces of three types PFRs in their urine. After a cycle of IVF treatments, those with high levels of the chemicals were 31% less likely to have the embryo successfully implant in the uterus, 41% less likely to achieve pregnancy, and a 38% less likely to have a live birth than those with low levels.

What do the results mean? The research team looked at the correlation between traces of PFR and pregnancy outcomes but did not study whether PFR exposure was the cause of pregnancy complications.  Thus, we can’t conclude that exposure to PFR-containing products leads to infertility. However, the findings suggest an association between high levels of PFR exposure and poor pregnancy outcomes. Additionally, because researchers didn’t look at which specific PFR-containing products were the source of the chemical exposure, we can’t single out yoga mats or sofas as the culprits.

Are there limitations to the study?
The study participants were drawn from a small pool of women who were living in and around Boston, so it is not representative of the population at large. Plus, all participants were recruited from an IVF clinic, which suggests they many participants were predisposed to fertility issues coming into the study.

What’s next?
There’s an ongoing debate about the rational for putting flame retardants like PFRs in household products. Studies like this one provide compelling evidence for a potential association between PFR exposure and negative health outcomes like infertility, though more research needs to be conducted.  There are also questions as to how effectively PFRs prevent fires. In 2010, a group of 145 scientists from 22 countries published a statement detailing their concerns that flame retardants weren’t worth the health risks they posed.

What can people do to protect themselves in the meantime?
While it’s nearly impossible to fully avoid PFRs, consumers can minimize exposure by looking for products that have a natural flame retardant like leather or wool fabric, or seek out organic yoga mats. In a Huffington Post article, lead author Courtney Carignan of the Harvard T. Chan School for Public Health said that other precautions, like good-hand washing practices before meals, can also help lower levels of these chemicals in the body.

Evaluating the Impact of Cutbacks to HIV Programs in Resource-Limited Nations

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Proposed reductions in U.S. foreign aid would have a devastating impact on HIV treatment and prevention programs in countries receiving such aid, an international team of investigators reports. In their paper published online in Annals of Internal Medicine, the team led by researchers at Massachusetts General Hospital and the Yale School of Public Health describes how a 33 percent cutback in funds earmarked for HIV/AIDS prevention, treatment and research in recent budget proposals would only save $900 per year of life lost in the countries of South Africa and Côte d’Ivoire.

Read the full press release here.