12 Days of Research at Mass General: Autism and the Blood-Brain Barrier

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In the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

February 2017:

Five Things to Know: The Blood-Brain Barrier, Intestinal Permeability and Autism

Researchers from the Center for Celiac Research and Treatment at Massachusetts General Hospital and the Mucosal Immunology and Biology Research Center at MassGeneral Hospital for Children (MGHfC) recently came out with a study published in Molecular Autism. Here are five things to know:

  1. Autism spectrum disorder (ASD) is the fastest-growing developmental disability in the U.S., with 1 in every 68 children born in this country diagnosed with ASD. Parents and researchers alike are looking for to learn more about the causes and develop new treatment options for this complex condition.
  2. The blood-brain barrier prevents materials in the blood from entering the brain, and the intestinal epithelial tissue (the intestine’s lining) creates a boundary between the intestine and the rest of the body. When either of these barriers aren’t functioning properly, it can cause inflammation.
  3. The research team analyzed postmortem brain tissues from 33 individuals (8 with ASD, 10 with schizophrenia and 15 healthy controls) and intestinal tissues from 21 individuals (12 with ASD and 9 without such disorders).
  4. The results showed alterations in blood-brain barrier and intestinal permeability in individuals with ASD. This is the first time anyone has shown that an altered blood-brain barrier and impaired intestinal barrier could both be contributing to inflammation in the nervous system tissue of individuals with ASD.
  5. What’s next? Researchers plan to look at how the composition of microbiota in the intestine impacts intestinal permeability and the behavior of autistic individuals. Researchers already know that kids with ASD have an altered composition of gut microbial communities. If they can learn more about this composition impacts ASD, they may be able to devise new treatments.

Learn more about this study here.

You can find the original post here.

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12 Days of Research at Mass General: She Watches Worms While They Sleep

Banner 12 days of researchIn the 12 days leading up to our holiday hiatus, we are looking back on the past year and sharing some highlights in Massachusetts General Hospital research news from each month of 2017.

January 2017:

Postdoc Profile: Hayley Mattison, PhD

mattison-banner.jpgOn a typical day, you will find me in the lab at my microscope taking images of neurons that ‘glow’ green in the brains of the microscopic worm, Caenorhabditis elegans (C. elegans).

As a postdoctoral fellow in the laboratory of Joshua Kaplan, PhD, in the Department of Molecular Biology at Massachusetts General Hospital, I study the neurons that control sleep in the worm. (Yes, worms sleep).

Worms have four larval stages between hatching and adulthood, and they undergo a sleep-like state called lethargus prior to entering each stage.

Sleep is thought to have a role in biological processes such as growth and development in animals, including humans and worms. But what happens in the brain to allow and maintain the state of sleep is not entirely understood, which is why a simple model system like the worm is a great place to start.

Worms have a small and well-characterized nervous system consisting of only 302 neurons. The connections between these neurons have been completely mapped so learning about the circuits, or neural networks, that control behaviors is simpler than in more complex organisms.

In contrast, humans have billions of neurons and trillions of synapses. Scientists have started to map these connections, but it will take many more years of research to achieve the complete picture.

Worm genetics are also much simpler than other animals because C. elegans exist primarily as self-fertilizing hermaphrodites, meaning they produce both sperm and eggs and can reproduce independently of a mate. Therefore, new or modified DNA can be introduced into worms to alter the expression of genes in their offspring, which allows us to create new strains of worms with relative ease.

These new strains of worms can be designed to express certain proteins in individual neurons, and/or to make the neurons glow green for imaging experiments. This helps us to identify the neurons that have a role in behaviors, such as sleep.

Just like humans, worms do not interact with their environment when they are asleep, because their sensory neurons are not able to respond to external cues such as the presence of food or odors. This is because sensory neurons are being “silenced” by the action of neuropeptides in the brain that promote the sleep state.

Neuropeptides are hormone-like chemical messengers that are released by one set of neurons to affect another set of neurons. To wake the worm up, other neuropeptides are released to wake up, or “arouse,” the worm by allowing their sensory neurons to become active again. Once awake, the worms can respond to their environment and resume normal activities such as eating and mating.

The Kaplan lab is interested in identifying which neurons play a role in this process, and the mechanisms these neuropeptides employ to create the sleep and arousal states.

We have already identified a circuit of neurons associated with sleep and arousal in worms. The goal of my project is to find additional neurons that function in this circuit, and then learn how these neurons communicate to regulate these behavioral states.

As a neuroscientist, I have always been fascinated by the complexity of the nervous system and how much is still unknown about how the brain works. Understanding the nervous system of a “simple” organism such as C. elegans can help us to deconstruct basic functions of the brain in more complex organisms.

Down the road, what we discover about worm sleep could be applicable to humans and lead to therapies that promote sleep in the brain. These tiny worms have a lot to tell us about our own brains. Even in their sleep.

You can find the original article here.

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Gatchel Untangles the Causes of Mood and Anxiety Symptoms and Loss of Brain Function in Aging Populations

Jennifer Gatchel studying Alzheimer's disease

Massachusetts General Hospital researcher Jennifer Gatchel, MD, PhD, is using brain imaging technology to learn more about the connections between mental illness and cognitive decline in aging populations.


Often referred to as the golden years, life after retirement can sometimes turn out to be less than sunny.

Dramatic lifestyle changes such as admittance to an assisted care facility and loss of mobility or independence can take a toll on mental health.

In fact, twenty percent of people over 55 suffer from a mental disorder, and two-thirds of nursing home residents exhibit mental and behavioral problems.

As a geriatric psychiatrist at Massachusetts General Hospital and McLean Hospital, Jennifer Gatchel MD, PhD, works with adults ages 60 and over to help them cope with life’s transitions.

For many of her patients, symptoms of mental illness are often compounded by symptoms that indicate the onset of degenerative conditions like Alzheimer’s disease.

“These are conditions I see every day in my practice that I find highly compelling,” says Gatchel. “Could psychiatric symptoms in older adults be driven in part by Alzheimer’s disease pathology and proteins impacting brain circuitry? If so, it would represent an important shift in the way we think about treating older adults presenting with these symptoms.”

Gatchel is using a combination of neuroimaging, cognitive testing, clinical assessments, and her ongoing interactions with patients to inform her research on the relationships between mood and anxiety symptoms and dementia.

She ultimately hopes to improve care and brain health for older patients and help them make the most of their golden years. Continue reading “Gatchel Untangles the Causes of Mood and Anxiety Symptoms and Loss of Brain Function in Aging Populations”

Weekend Links

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We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

This Badass Researcher is Using Brain Mapping to Improve Anxiety and Depression Treatment for Teens – Congratulations to Mass General’s Anastasia Yendiki, PhD, whose research was featured in InStyle Magazine’s Badass Women article series. Dr. Yendiki is developed a brain-mapping tool called TRACULA that helps to decipher white-matter pathways.  She is studying the brain scans of adolescents with depression and anxiety disorders to identify ways in which their white matter structure differs from those of healthy control subjects. Dr. Yendiki, who conducts her research at the Martinos Center for Biomedical Imaging, was also named one of Fast Company’s Most Creative People in Business for 2017.

Doctor out sick? A substitute physician is no worse for patients’ health – A study led by Massachusetts General Hospital/Harvard Medical School physicians finds that temporary, “locum tenens” physicians provide the same level of care as regular hospital staff.

A Psychological Explanation for Kids’ Love of Dinosaurs

Could this be the first prescription video game? New data show it helps kids with ADHD

The Top 10 Websites for Science in 2017

Study Predicts Alzheimer’s Cases to Double in US by 2060. How Mass General Researchers are Fighting Back.

Alzheimer's disease crumbling brainScientists at the National Institutes of Health (NIH) released some unsettling new estimates about the number of individuals affected with Alzheimer’s disease this week—and how that number is expected to skyrocket in the near future.

The NIH team estimates that there are 6 million Americans who currently have either Alzheimer’s disease or some form of cognitive impairment, and that number is expected to more than double to 15 million by 2060.

These staggering statistics highlight the pressing need to better understand how and why Alzheimer’s disease develops, as well as how to treat it.

Here are just some of the ways researchers at Massachusetts General Hospital are working on new strategies to improve diagnosis and treatment.

How “Alzheimer’s in a Dish” Could Improve Research and Treatment Efforts

Scientists and clinicians at Mass General’s Institute for Neurodegenerative Disease (MIND) have developed a creative solution to overcome the challenges of modeling Alzheimer’s disease in the lab.

The laboratory teams of Doo Yeon Kim, PhD, an investigator in the Genetics and Aging Research Unit at MIND, and Rudy Tanzi, PhD, have found a way to grow human neural stem cells in a three-dimensional gel matrix.

One of the challenges in studying the progression of Alzheimer’s disease in the laboratory is that the brain exists in three-dimensions. A Petri dish is flat. Thus it has been difficult to replicate the disease solely by culturing neuronal stem cells and growing them in a dish.

The new 3D model is capable of housing and supporting neuronal stem cells that have been genetically engineered to develop the same plaques and tangles found in the genetic form of Alzheimer’s disease.

The gel not only provides a more brain-like environment for the neurons, allowing them to create more connections, it also helps to retain the Alzheimer’s-linked proteins that are produced by the genetically engineered neuronal cells.

This new model could represent a big step forward in Alzheimer’s research, as it will allow investigators to test thousands of chemical compounds against a more realistic model of the disease, which could speed development of new therapies.

Learn more

Scent Recognition and Recall Test Could Better Predict Onset of Alzheimer’s Disease

A Mass General research team, led Mark Albers, MD, PhD, of the Center for Alzheimer’s Research, has developed a series of four tests designed to measure early indications of Alzheimer’s disease based on an individual’s ability to recognize, remember and distinguish among odors.

The 30-minute scent test was given to 183 people between 60 and 80 years old – some with mild cognitive impairment or possible Alzheimer’s disease—and of those, about 20 percent showed signs of olfactory deficiencies.

Genetic and imaging testing revealed that that these same individuals had other deficiencies that have been linked to the illness, including thickening of certain brain structures and a mutation in a gene associated with increased risk of Alzheimer’s disease.

Learn more

New Brain Scans Used to Detect Risk

Researchers at the Martinos Center for Biomedical Imaging are using a computer aided system called BrainPrint to analyze MRI brain scans to help distinguish individuals who are having minor memory issues from those who are in the silent, early stages of Alzheimer’s disease.

The research, led by Martin Reuter, PhD, has shown there are more pronounced asymmetrical differences in the shapes of critical structures between the left and right sides of the brain in individuals who are later diagnosed with Alzheimer’s.

A better understanding of the early signs of Alzheimer’s could improve detection and treatment strategies, and delay or prevent the significant cognitive decline that occurs in later stages of the disease.

Learn more

Non-Invasive Imaging Techniques Help Researchers See Tau and Amyloid Development

Jorge Sepulcre, MD, PhD, and team at Mass General’s Gordon Center for Medical Imaging have been working to improve noninvasive tests to detect amyloid plaques and tau tangles. Specifically, they are investigating the pathways through which tau spreads and amyloid builds up over time.

Their research has found that the tau and amyloid proteins use different brain pathways to reach the areas where they accumulate.

These findings could help researchers describe the stage of the disease in a given patient and may improve their ability to track responses to potential therapeutic interventions, says Sepulcre.

Studying A Small Group in South America Could Help Alzheimer’s Patients Worldwide

The Familial Dementia Neuroimaging Lab, led by Yakeel T. Quiroz, PhD, is investigating how brain changes may lead to memory loss or dementia later in life. Their research is focused on a large group of related individuals Colombia who carry a genetic mutation that predisposes them to develop an inherited form of Alzheimer’s disease.

“If our findings only apply to our population from Colombia, we will still help thousands of people”, says Edmarie Guzman-Velez, PhD, a postdoc in Quiroz’s lab. “But if what we find can also be applied to those who develop sporadic (non-hereditary) Alzheimer’s disease, we could help millions of people around the world.”

Proteins Take Shape with New Technology

The 2017 Nobel Prize in Chemistry went to three scientists for their development of a new technology called cryo-electron microscopy (cryo-EM). This technique freezes proteins, and bombards them with electrons, allowing researchers to observe the building blocks of human cells.

In a recent podcast by Proto, Luke Chao, PhD, a researcher in the department of molecular biology at Massachusetts General Hospital, discussed the significance of cryo-EM and how this basic science technique could help advance clinical treatment.

Proteins as seen through cryo-EM
Over the last few years, researchers have published atomic structures of numerous complicated protein complexes. a. A protein complex that governs the circadian rhythm. b. A sensor of the type that reads pressure changes in the ear and allows us to hear. c. The Zika virus

Chao explained that cryo-EM provides scientists with an opportunity to better see the shapes of molecules. Proteins, such as hemoglobin and antibodies, are versatile molecules and their shapes can provide a lot of insight into how they work and their function. Understanding their function is especially important if researchers want to develop a therapy to modify or block its role.

Cryo-EM offers an advantage over previous microscope-based techniques because it allows scientists to see the protein in more shapes and stages of motion.

Think of how difficult it can be to take a good photo of fireworks, for example. Similarly, proteins are dynamic, moving molecules and cryo-EM allows scientists to get more snapshots of them in motion.

Cryo-EM resolution

Listen to the entire podcast episode on the Proto website.

(top photo courtesy of the Nobel Prize; bottom photo courtesy of the Nobel Prize- MARTIN HÖGBOM/THE ROYAL SWEDISH ACADEMY OF SCIENCES)

 

 

 

Four Mass General Investigators Recognized with Endowed Chairs

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Massachusetts General Hospital recently established four endowed chairs. Meet the four investigators whose work and contributions have been recognized through their appointment to these roles and please join us in congratulating them!


Marlene FreemanMarlene Freeman, MD, associate director of the Mass General Ammon-Pinizzotto Center for Women’s Mental Health and the Department of Psychiatry, was appointed the inaugural incumbent of the Abra Prentice Foundation Endowed Chair in Women’s Mental Health.

“It is such an honor for me to be the recipient of this generous gift to our program, department and hospital.  I am grateful to Mrs. Wilkin and her foundation trustees for this incredible gift.  The enduring fund provided by this Chair will allow me to continue to do work that I am passionate about and that ultimately I believe will help and empower large numbers of women and their families.”


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Moussa Mansour, MD, director of the Atrial Fibrillation Program at Mass General, received the inaugural Jeremy Ruskin, MD, and Dan Starks Endowed Chair in Cardiology.

“I feel very fortunate to be the recipient of the Jeremy Ruskin and Dan Starks endowed Chair in Cardiology. Dr. Ruskin is my mentor and he is a pioneer and one of the founders of modern cardiac electrophysiology. Dan Starks is a visionary and his strategies in the companies that he lead resulted in the development of new technologies that saved the lives of millions of people. Being named to a chair that holds the names of these two individuals is a great honor.”


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Patrick L. Purdon, PhD, associate director of the Mass General Neuroscience Statistics Research Laboratory, was honored as the inaugural incumbent of the Nathaniel M. Sims, MD, Endowed Chair in Anesthesia Innovation and Bioengineering.

“I’m thrilled to be the recipient of the Sims Chair. Nat Sims has been a hugely influential mentor for me in my efforts to translate neuroscience and engineering advances into medical innovations. I’m also greatly indebted to my colleagues in the Department of Anesthesia, Critical Care and Pain Medicine, and at MGH as a whole, most notably my long-time mentor and colleague Emery Brown. The collaborative and creative culture at MGH has been a huge part of my success. The support provided by the Sims Chair will help me pursue exciting new research on brain dynamics in aging and child development, and to develop new technologies to improve brain health and to help treat opioid overdose patients.”


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Pictured from left: Britain Nicholson, MD, senior vice president for Development; Thomas Brady, MD, vice chairman of MGH Radiology Research and the chair’s donor; Wedeen; James Brink, MD, MGH radiologist-in-chief

Van Wedeen, MD, of the Athinoula A. Matrinos Center for Biomedical Imaging, has been appointed as the inaugural incumbent of the Thomas J. Brady, MD, Endowed Chair in Radiology.

Weekend Links

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We’ve hand-picked a mix of Massachusetts General Hospital and other research-related news and stories for your weekend reading enjoyment:

Kill Switches – Scientists have designed “suicide switches” to ensure that lab-made organisms don’t go rogue

New York City Has Genetically Distinct ‘Uptown’ and ‘Downtown’ Rats – A graduate student sequenced rats all over Manhattan, and discovered how the city affects their genetic diversity.

Telemedicine For Addiction Treatment? Picture Remains Fuzzy

So much for the abominable snowman – Study finds that ‘yeti’ DNA belongs to bears

Want to challenge your science communication skills? Try writing a haiku! 

A holiday gift guide for all the science lovers on your list

(top photo courtesy of NPR – Andy Baker/Ikon Images/Getty Images)

World AIDS Day 2017

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World AIDS Day takes place on the 1st of December each year. It’s an opportunity to highlight the success of worldwide efforts to combat HIV/AIDS, as well as the importance of continued support for these efforts.

Researchers and clinicians, including those at Massachusetts General Hospital, acknowledge that although great strides have been made in the clinical treatment of HIV over the past three decades, there is still work to do.

In recognition of World AIDS day, we have collected some recent stories about the ways Mass General investigators are working to expand our knowledge of the virus, reduce transmission rates, improve health outcomes for HIV-positive patients and advance treatment.

The Ragon Institute

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The Phillip T. and Susan M. Ragon Institute was established in February 2009 at Mass General, MIT and Harvard with the dual mission of contributing to the accelerated discovery of an HIV/AIDS vaccine and subsequently establishing itself as a world leader in the collaborative study of immunology. Learn more about their exciting research efforts.

Exploring the Risks of Cardiovascular Disease in HIV-positive Women

sara looby.pngSara Looby, PhD, ANP-BC, FAAN, is a Nurse Scientist at the Yvonne L. Munn Center for Nursing Research, an Assistant Professor of Medicine at Harvard Medical School, and a Principal Investigator in the Program of Nutritional Metabolism at Mass General. Through her research efforts, Looby is investigating how HIV might influence the development of conditions such as heart disease and the increased risk for heart attacks that tend to impact HIV-positive populations at an earlier age compared to non-infected populations. Learn how she’s using a patient-centered approach to reduce cardiovascular disease risk for HIV-positive women.

Levison Makes a Dramatic Bid to Improve HIV Care Compliance

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Julie Levison, MD, MPH, MPhil, FACP, is a clinician-investigator in the Division of General Internal Medicine at Mass General, an Assistant Professor of Medicine at Harvard Medical School, and a bi-lingual (Spanish-English) infectious disease physician at MGH Chelsea HealthCare Center. Levison and her team have created a dramatic video illustrating the consequences of letting HIV care lapse. The video is part of a research project designed to improve outcomes in one subset of the HIV patient population—migrants from Puerto Rico and Latin America. Watch the video and learn how it could potentially improve HIV care adherence by Latino immigrants.

The Health Hazards of Smoking in HIV-positive Populations

196368.jpgKrishna Reddy, MD, is a physician in the Division of Pulmonary and Critical Care Medicine and the Medical Practice Evaluation Center at Mass General. His research focuses on comorbidities in people living with HIV, including smoking-related diseases and tuberculosis. He recently led a study that found people with HIV who smoke are more likely to die from lung cancer than from HIV itself. Read more about the study and its implications.

(top photo courtesy of The Ragon Institute)

Research Awards and Honors: November 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:

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Charumathi Baskaran, MD, of the Pediatric Endocrine Unit; Laura Dichtel, MD, of Neuroendocrinology; and Vibha Singhal, MD, of the Pediatric Endocrine Unit, were each honored with an Early Investigator Award from the Endocrine Society. Baskaran and Dichtel received their awards for endocrine research, and Singhal received his for metabolic bone research. The awards were established to recognize the achievement of early career investigators in endocrine research. The awardees be honored at the Endocrine Society’s 100th Annual Meeting & Expo next March in Chicago.

“It is a wonderful honor to have been selected as an Early Investigator Awardee through the Endocrine Society. Awards like this one are incredibly important to recognizing and supporting junior investigators as we build our independent research careers. I am grateful to the Endocrine Society for continuing this program of honoring and supporting young investigators. I am additionally grateful to Dr. Karen K. Miller, my research mentor here at MGH, who is truly dedicated to training the next generation of clinical researchers.” – Laura Dichtel, MD

“It was very encouraging to receive the Early investigator Award from the Endocrine Society. Not only did it provide funds for travel and meeting attendance but also provided the moral boost that keeps a young investigator like myself going. I am thankful for the opportunity to be working at MGH which amalgamates the best resources and mentorship. I am looking forward to making some contribution to advancing science.” – Vibha Singhal, MD

“As a member of the faculty at the Pediatric Endocrine Unit, my research focuses on investigating the impact of hormonal changes on mood and behavior in adolescents and young children.  This recognition in the from Endocrine society in the form of  ‘Early Investigator Award’ is a great honor and a big moral boost for me. Endocrine Society offers a platform for budding researchers like me to showcase our findings to their entire professional community. This award had opens up a whole new area of networking and will allow me to develop collaborations with the leading researchers in my areas of interest. The Early Investigator Award will enable advancement in my research career and will keep me motivated to pursue my goal against all odds.” – Charumathi Baskaran, MD


Cudkowicz.jpgMerit Cudkowicz, MD, chief of the Neurology Service, has received the American Academy of Neuromuscular and Electrodiagnostic Medicine Honorary Membership Award. This award recognizes a nonmember physician who is a major contributor to the field of Neuromuscular disease through teaching, research and/or scholarly
publications.

“I was honored to receive this lifetime award from the AANEM. Neuromuscular specialists are physicians who excel at both care and research of people with a large variety of disorders, including ALS. While not personally trained in electrodiagnostics, I have worked closely with my neuromuscular colleagues to develop new treatments and improve the care of people with ALS. Many neuromuscular physician scientists are leaders in clinical trials and are making a huge difference in the lives of our patients. I am proud to be part of this collaborative network of physicians and other healthcare providers.”


Daly.jpgMark Daly, PhD, chief of the Analytical and Translational Genetics Unit, has been named as one of the new members of the National Academy of Medicine. Election to the Academy is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service. New members are elected by current members through a process that recognizes individuals who have made major contributions to the advancement of the medical sciences, health care and public health.

“I am humbled and honored to receive this recognition and look forward to contributing to the National Academy of Medicine. Genetics today is truly a team sport and my part is just one of very many – therefore I am gratified not by the personal recognition, but that it reflects that our global, collaborative partnerships in genetic research are making real progress that will advance medicine.”


Walker.jpgMelissa Walker, MD, PhD, has received the 2017 Shields Research Grant from the Child Neurology Foundation. The award supports translational or basic research by a child neurologist or developmental pediatrician early in his/her academic career and who has developed clinical research skills and has a plan for further development of that research or has basic science research skills related to child neurology and who has a plan to translate the new knowledge into clinical care for children with neurologic diseases.

“I’m honored to receive the Shields Award to support my translational and basic science research in the laboratory of Dr. Vamsi Mootha. Primary Mitochondrial Disorders are a group of individually rare but collectively significant diseases exhibiting remarkable clinical and genetic heterogeneity. Currently, no reliable biomarkers or clinical tests exist for diagnosis or disease monitoring. We aim to develop a reliable, rapid, inexpensive, and noninvasive assay of mitochondrial function. As Director of the MGH Pediatric Mitochondrial Disorders Clinic, this award will allow me to conduct this potentially transformative work in a world-class laboratory while concurrently caring for affected patients.”