How a 3D Model of Alzheimer’s Disease is Providing New Hope in the Search for Treatments

Reigning in Alzheimer’s disease continues to be a challenge — more than 10 million families are affected by this degenerative neurological disease, and the number of patients dying from the disease has increased 68 percent since 2010.

In the past decade, attempts at developing drugs to slow or halt the progression of Alzheimer’s disease have been unsuccessful. The traditional path for early testing of promising therapies – mouse models – has been ineffective, and more than a dozen major clinical trials have failed.

But scientists and clinicians at Massachusetts General Hospital’s Institute for Neurodegenerative Disease (MIND) have developed an innovative new approach that could significantly improve the drug development process.  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.

This gel system allows the neural cells to grow more naturally and form into 3-D networks just like they do in the brain. It also provides a more accurate model of the signature plaques and tangles that develop around these neurons in Alzheimer’s disease.

The stem cells used in this lab model are genetically engineered to produce two proteins that are the hallmarks of Alzheimer’s disease – β-amyloid and tau. In the brains of people with Alzheimer’s, excessive accumulation of β-amyloid results in the formation of plaques in the spaces between neural cells, while tau is the main component of destructive neurofibrillary tangles within the cells.

Until Dr. Kim’s success, no single model of Alzheimer’s disease contained both amyloid plaques and neurofibrillary tangles. It usually takes a year to develop plaques in mouse models, it took only six weeks to develop both plaques and tangles in the “dish.”

Dr. Kim is now working with a consortium of labs to test thousands of FDA-approved drugs in this “Alzheimer’s in a dish” model to see if any of the drugs are effective in reducing levels of p-tau, a protein that is increased in Alzheimer’s patients.

Of the 2,400 drugs that have been tested, the team had approximately 40 promising hits that they can now investigate further.

Learn more: https://giving.massgeneral.org/fresh-alzheimers-approach-sparks-hope/

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:

For Some, Cutting-Edge ‘CAR-T’ Treatment Unleashes ‘Pac-Man’ Cells Against Blood Cancer

Gut Health May Begin in the Mouth

Why Precision Research May Lead To Blockbuster, Not Customized, Medicines

Mass. General Dilemma: Separate Conjoined Twins To Save One, Or Let Both Die?

Step Inside the Mind of the Young Stephen Hawking as His PhD Thesis Goes Online for First Time

Amazing Images From 2017 Photomicrography Competition

(top image: Immortalized human skin cells – 1st place winner of the 2017 Nikon Small World Contest [Source: Nikon Small World])

 

Health Literacy and Science Communication: Two Sides of the Same Health Communication Coin?

Did you know that October is Health Literacy month?

As part of this month-long focus on clear and understandable health information, the Massachusetts General Hospital Blum Center recently hosted a talk by Stacy Robison, MPH, MPCHES, co-founder of CommunicateHealth—a health education and communication firm—on the issues of health literacy in the digital age and how to create accessible content for adults with limited health literacy skills.

Health literacy is the degree to which individuals have the capacity to obtain, process, and understand basic health information and services needed to make appropriate health decisions. (2)

Considering that 72 percent of internet users looked up health information online in the last year, yet half of Americans read at an 8th grade level or below, there’s a clear need for digital health materials that all readers can understand, Robison said.

Robison also emphasized that we can’t write off low health literacy as a health disparity with no feasible solution — individuals in the healthcare field can play a role in addressing the issue by creating comprehensible tools and resources.

She provided the following three strategies for making easier to use materials:

  1. Create content that’s relevant and actionable: Put the most important information first and prioritize behaviors. For example, a webpage titled, “How to prevent asthma at home” is more actionable and appealing to readers than a webpage called “About asthma.”
  2. Display content clearly: Use bullets and short lists (like this one!), and avoid paragraphs with more than three lines of text. Robison’s research has shown that individuals with low literacy levels tend to skip over large chunks of text.
  3. Engage users: Take advantage of the capabilities of digital platforms to create content that’s interactive and shareable, and that uses videos or graphics to illustrate a point when appropriate.

What does this mean for the medical and scientific research community? We here at the Mass General Research Institute are big supporters of good science communication and see many overlaps in the principles of health literacy and the principles of science communication.

Our goal is to provide you with the essentials of a research study in short, easy to digest posts. We try to set the context to help you understand what the research means, and put the big takeaway at the top of the post. We also use different formats such as “five things to know” lists and Q&A to make the information easier on the eyes.

Let us know how we’re doing! What could we do better? What science resources do you look to?

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Research Awards and Honors: October 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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Deepak Balani, DMD, PhD, research fellow in the Endocrine Unit, has received the 2017 American Society for Bone and Mineral Research (ASBMR) Young Investigator Award. The award recognizes young investigators who submit top-ranking abstracts to an ASBMR Meeting. Balani received the award and a plaque at the ASBMR annual meeting in September.

“ASBMR is one of the top scientific societies primarily established to bring together clinical and experimental scientists involved in the study of bone and mineral metabolism. ASBMR organizes an annual meeting that invites top scientists from all over the globe. Getting chosen as one of the top abstracts and presenting my work in front of such a talented audience is very gratifying. For years Endocrine Unit of the Massachusetts General Hospital has been at the forefront of bone biology research. I am extremely happy that I have taken part in continuing this tradition.”

 

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Alex Soukas, MD, PhD, of the Diabetes Unit and the Center for Genomic Medicine, has received the Glenn Award for Research in Biological Mechanisms of Aging. The award provides unsolicited funds to researchers investigating the biology of aging. The mission of the Glenn Foundation for Medical Research is to extend the healthy years of life through research on mechanisms of biology that govern normal human aging and its related physiological decline, with the objective of translating research into interventions that will extend healthspan with lifespan. Soukas will use this award to continue his work in understanding the genetic mechanisms of aging and aging-related diseases.

“I received notification of the award by email during a meeting with a Harvard PhD student in my laboratory. Normally I wouldn’t open email during a meeting, but saw the title “Glenn Award” and could not resist. There are few moments in science when one feels like cheering out loud in science, and this was certainly one of them. I was surprised, amazed, and humbled to have been given such a great honor as the Glenn Award. The funding from this award will jump start our research aimed at promoting healthy aging in humans.”

 

Marc Wein.jpgMarc Wein, MD, PhD, of the Endocrine Unit, has received the 2017 American Society for Bone and Mineral Research Rising Star Award for his research, “Dissecting the roles of class IIa HDACs in osteocyte biology.” This award provides funding to promising young scientists and physician-scientists in the bone field who have already been recognized by individual National Institutes of Health “K awards” and other similar international professional development programs.

“I was thrilled to receive the 2017 Rising Star Award from the American Society for Bone and Mineral Research. I’m an endocrinologist interested in bone biology and new therapeutics for osteoporosis. The ASBMR has recognized the immense value of additional grant support for junior faculty starting independent research programs. This generous award will allow us to pursue ambitious studies on bone cell function that will identify new genes and pathways relevant to osteoporosis drug development. I’m deeply grateful for this award and the recognition by the ASBMR.” 

Wireless Sleep Monitoring System Could Make Sleep Studies Much Easier

If you find yourself tossing and turning all night, or hitting snooze a few too many times each morning, you’re not alone. More than 50 million Americans suffer from sleep disorders, and these sleep issues can get worse in individuals with Parkinson’s and Alzheimer’s disease.

Researchers from MIT and Mass General recently unveiled a wireless, portable system for monitoring individuals during sleep that could provide new insights into sleep disorders and reduce the need for time and cost-intensive overnight sleep studies in a clinical sleep lab.

Here are five things to know:

  1. Sleep disorders are typically diagnosed by bringing a patient into an overnight sleep lab, hooking them up to electrodes, and monitoring their brain activity while they sleep. While this process is effective, it is also limiting. Individuals with sleep disorders may have even more difficulty sleeping when they are hooked up to wires and in the artificial setting of a sleep lab.
  2. To make it easier to diagnose and study sleep problems at home, researchers at MIT and Mass General have created a new system for measuring sleep that is wireless, portable and powered by artificial intelligence.
  3. The system consists of a laptop-sized device that emits low frequency radio waves while an individual is sleeping. The device then measures changes in those waves that are caused by shifts in movement and breathing patterns in sleeping individuals. The device then uses an advanced algorithm—powered by artificial intelligence—to translate these changes into the different stages of sleep, including light, deep and rapid eye movement (REM).
  4. In a test of 25 healthy volunteers, the new system proved to be 80 percent accurate in identifying sleep stages, which is comparable to the accuracy of a sleep specialist reading EEG measurements, according to the research team
  5. The team is now planning to use their system to investigate how Parkinson’s disease affects sleep. Future research projects could look into common sleep disorders such as insomnia and sleep apnea, investigating how sleep is affected by Alzheimer’s disease, and detecting epileptic seizures that occur during sleep.

Researchers involved in this work are Dina Katabi, the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science at MIT, Matt Bianchi, chief of the Division of Sleep Medicine at Mass General, and Tommi Jaakkola, the Thomas Siebel Professor of Electrical Engineering and Computer Science at MIT. Mingmin Zhao, an MIT graduate student, is the paper’s first author, and Shichao Yue, another MIT graduate student, is also a co-author.

Source:

New AI algorithm monitors sleep with radio waves (MIT News)

Image credit: Christine Daniloff/MIT

Weekend Research 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:

Everyday bumps injured her joints, but finding the reason took half a century (STAT article written by Mass General physician Allison Bond)

Just ‘baby blues’ or postpartum depression? New app screens new mothers

This stretchy implant could help kids avoid repeated open-heart surgeries

TED Radio Hour: Citizen Science – TED speakers share how ordinary citizens are helping make groundbreaking discoveries in scientific research

And if you missed HUBweek, here’s a quick glimpse at last week’s takeover of City Hall Plaza:

 

(top photo courtesy of NPR – golubovy/Getty Images/iStockphoto)

Liquid Biopsies Give Clues on When and Why Cancer Treatments Lose their Efficacy

With the advent of targeted cancer therapies and immunotherapy, and with new CAR-T therapies on the way, more cancer patients are living with their disease. However, many cancer patients find that their therapies have limitations and are faced with the potential of disease progression. Often, those who initially respond to a course of treatment eventually develop a resistance to these medications, forcing oncologists to switch therapeutic course.

Currently, one of the ways to know when a treatment stops working is by taking a biopsy of the tumor. These surgical procedures are invasive and costly, and because they can only be done sporadically, valuable treatment time can be lost. Additionally, some cancer patients may be too physically fragile for surgery.

Researchers have been looking for a safe, fast, less expensive and more accurate way to identify early signs of treatment resistance, while also searching for new insights into the genetic changes that occur within tumor cells to drive this resistance. This way, new therapy plans can be considered sooner, giving the patient a better chance for their best possible outcome.

A new diagnostic blood test known as a liquid biopsy has shown early promise in addressing these needs. Now researchers, including a team from the Mass General Cancer Center, are providing confirmatory data that may help to move liquid biopsies into clinical practice. These data were presented at the ESMO 19th World Congress on Gastrointestinal Cancer.

How do liquid biopsies work?

A liquid biopsy is a diagnostic test that detects circulating tumor DNA (ctDNA), which is genetic material released by dying tumor cells that flows through the bloodstream. These tests are less invasive than a tissue biopsy and therefore can be given with greater frequency.

Regularly monitoring ctDNA levels in a patient’s bloodstream can provide early notice when a treatment is no longer working. It could also offer a more complete picture of the genetic changes in tumor cells that are driving the resistance to treatment, which could guide new treatment courses.

Liquid biopsies and gastrointestinal cancer study

Mass General Cancer Center investigators followed nearly 40 patients with various forms of gastrointestinal cancers who had experienced initial success with targeted therapies, but then began to show signs of treatment resistance. Liquid biopsies were taken when the patients’ disease started to progress to analyze the levels and genetic profile of ctDNA in their bloodstream. Researchers identified one or more mutations or mechanisms that contributed to treatment resistance in 31 of the 40 patients. Fourteen of these patients had multiple mutations that contributed to resistance.

In patients who had both solid tissue biopsies and the liquid biopsies, the researchers found that in two-thirds of the cases, the liquid biopsies revealed the presence of more genetic mutations than tissue biopsies alone.

“Identifying what specific mutations are responsible for treatment resistance is very important in helping clinicians choosing what treatment path a patient should try next, whether it be another drug or perhaps radiation,” said study investigator Aparna Parikh, MD, from the Mass General Cancer Center.

“We have shown this approach is feasible across many different GI cancers,” she noted. “The next step is to study how best to use this new technology in daily practice. It’s important for clinicians to understand its utility as well as its limitations.”

Meet our Fall Communications Intern!

Please join us in welcoming Nishtha Yadav, a graduate student at Emerson College and our communications intern this semester. Be sure to check back here for updates on what she’s working on!

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Name

Nishtha Yadav

Where do you attend school and what’s your major, and year?

I’m a second year Communication Management graduate student at Emerson College.

Where are you from?

I currently live in Brookline, but I’m originally from New Delhi, India.

Why are you interning at the Mass General Research Institute?

I wanted to get a glimpse of how a leading research institute pushes out information to their stakeholders about clinical trials and research conducted at the hospital and its affiliates. As someone who enjoys writing long-form, research-oriented articles and has an avid interest in learning more about the healthcare industry, this internship was a perfect fit for me.

What do you hope to gain or learn while interning here?

Previously, I worked as a reporter with a leading English daily in India and did not get an opportunity to write research based articles due to the 24/7 news cycle. So, I hope I’m able to strengthen my research and writing skills.

Also, by the end of my internship, I hope I’ve a better sense of scientific/health industry terminology, which would help me in understanding complex research being conducted by scientists and clinicians.

Why are you interested in health communications?

This summer, I interned at Dana-Farber Cancer Institute and had an opportunity to be a part of their radio-telethon, where all the patients, researchers and doctors were present to raise funds for cancer research. I saw patients, right from babies to octogenarians, and their families who couldn’t stop thanking their doctors for saving their lives. That’s when I realized that communicating with the public about medical breakthroughs and treatments is of utmost importance – it can save lives!

What are your future/career goals?

I would like to work either in the nonprofit sector or work as a crisis management professional. Years from now, I also see myself running for public office in India.

Secretly, I’m hoping that I’ll be discovered by Ryan Murphy and become the next Sarah Paulson! (Murphy is the creator of the American Horror Story, Glee, People vs. O.J. Simpson, etc., and Paulson is an award-winning actress, famous for her work in the American Horror Story and People vs. O.J. Simpson)

What do you like to do when you’re not being an intern?

Apart from planning my Oscar acceptance speech and binge-watching Netflix, I try to listen to as many podcasts as I can and read as much as I can, while trying different varieties of herbal tea.

Favorite dinosaur?

Dino from The Flintstones. Just kidding! Argentinosaurus is my favorite dinosaur. I always get the sense that they were free-willed and walked around their natural habitat like a king/queen.

Favorite food?

My mother has an elaborate recipe for cottage cheese (called Paneer in South Asia) – it’ll always be my favorite food.

HUBweek Art of Talking Science Competition Recap

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Last Wednesday the Mass General Research Institute hosted The Art of Talking Science: Rise of the Machines at the Russell Museum at Massachusetts General Hospital.

As part HUBweek’s weeklong festival, this science communication competition challenged researchers focused on artificial intelligence, machine learning and digital health to present their science in four minutes or less. Each contestant received feedback from a panel of celebrity judges and, at the end, one presenter was crowned the winner.

Here’s a look back at some of the highlights from the afternoon:

Opening Remarks

Sue Slaugenhaupt, PhD, Scientific Director of the Research Institute, gave an introduction on the importance of communicating science.

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Sue Slaugenhaupt, PhD

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Meet the Judges

Dr. Slaugenhaupt also introduced our panel of judges who each spoke for a few minutes about what science communicating means to them.

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Our amazing judges, were (from left): Ike Swetlitz, Reporter for STAT News, Rich Hayes, Creative Director/Deputy Director of Communications for the Union of Concerned Scientists, Carey Goldberg, Editor for the WBUR CommonHealth Blog, and Christine Reich, PhD, Vice President of Exhibit Development and Conservation at the Museum of Science, Boston.

Keynote Presentation

Then judge Christine Reich gave a keynote presentation discussing how the Museum of Science empowers their guests through science communication.

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Christine Reich, PhD

After Dr. Reich’s fascinating presentation, the competition began!

The Competition

Justin Baker, MD, PhD, went first with his presentation, Exploring the Human-Human Interface. Dr. Baker is Scientific Director at the Institute for Technology in Psychiatry and an Assistant Psychiatrist at McLean Hospital.

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Justin Baker, MD, PhD

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Kamal Jethwani, MD, MPH, Senior Director of Connected Health Innovation, Partners Connected Health, then gave a slideless presentation entitled, Want to Lose 5 Lbs Fast? Artificial Intelligence Holds the Key.

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Kamal Jethwani, MD, MPH

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Our third presenter was Jacob Dal-Bianco, MD, who spoke about preventing rheumatic heart disease. Dr. Dal-Bianco is a cardiologist at Massachusetts General Hospital.

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Jacob Dal-Bianco, MD

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David Gow, PhD, of the Cognitive/Behavioral Neurology Group at Massachusetts General Hospital, then gave his presentation, Using Machine Learning to Help the Brain Understand Itself.

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David Gow, PhD

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Up next was Lisa Gualtieri, PhD, ScM, who discussed a lending library for fitness trackers. Dr. Gualtieri is the founder of Recycle Health, an Assistant Professor in the Department of Public Health and Community Medicine at Tufts University School of Medicine, and the Director of the Digital Health Communication Certificate Program.

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Lisa Gualtieri, PhD, ScM

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Closing out the program was Roland Carlstead, PhD, of the Developmental Biology Research Program at McLean Hospital. Dr. Carlstead discussed whether treatment works and if the placebo effect is real.

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Roland Carlstedt, PhD

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After much deliberation, the judges named Justin Baker as the winner.

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Thank you to all our contestants and the judges for their insightful feedback and support of science communication!

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Four Massachusetts General Hospital Researchers Receive Prestigious NIH Director’s Awards

Please join us in congratulating the four Mass General investigators who recently received director’s awards from the National Institutes of Health (NIH)! These awards are given to exceptionally creative scientists who propose innovative approaches with high-impact potential to major challenges in biomedical research.

Continue reading to learn more about each researcher and their proposed work as well as their reaction to receiving this award.

New Innovator Award

The New Innovator Award supports exceptionally creative early career investigators who propose innovative, high-impact projects.

Evan Macosko, M.D., Ph.D.
Broad Institute of MIT and Harvard, Massachusetts General Hospital

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“I am delighted and honored that the NIH is willing to support this high-risk technology project.  The lab can’t wait to get started on some potentially very impactful scientific work.”

Project Title: Slide-Seq: High-Resolution In Situ Expression Profiling for Neuropathology
Grant ID: DP2-AG-058488

Evan Macosko is a principal investigator in the Stanley Center for Psychiatric Research at the Broad institute, and an Assistant Professor of Psychiatry at Harvard Medical School. His research focuses on developing and leveraging new technologies in genomics to characterize pathophysiological mechanisms in neuropsychiatric diseases. As a postdoc in Steven McCarroll’s lab at Harvard Medical School, he developed a new method, Drop-seq, for performing highly parallel gene expression analysis of single cells from complex neural tissues. He completed a psychiatry residency at MGH and McLean Hospital, and is currently an attending psychiatrist at MGH. He holds a Ph.D. in Neuroscience and Genetics from Rockefeller University, and an M.D. from Weill Cornell Medical College.

Radhika Subramanian, Ph.D.
Massachusetts General Hospital and Harvard Medical School

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“I am extremely grateful and honored to receive the NIH Director’s New Innovator Award. The support provided by this award will allow my lab to pursue a new research direction where we will develop a versatile cell-free imaging platform that will enable us to decipher how spatial cues are encoded and decoded within cells. We expect that the toolkit established here will be applicable for elucidating the fundamental mechanisms that govern the spatial organization of cellular reactions that underlie diverse cell-­biological  processes of biomedical significance such as cell division, migration, and development.”

Project Title: A Versatile Platform for Reconstructing the Spatial Organization of Intracellular Signaling During Cell-Division
Grant ID: DP2-GM-126894

Radhika Subramanian is an Assistant Professor in the Department of Molecular Biology at Massachusetts General Hospital and the Department of Genetics at Harvard Medical School. Her lab focuses on elucidating the fundamental principles by which intracellular spatial organization on the micron-length scale is achieved by the collective activity of nanometer-sized proteins. Radhika received her M.Sc. in Chemistry from the Indian Institute of Technology in Delhi, India. She performed her doctoral research with Dr. Jeff Gelles at Brandeis University followed by postdoctoral training in the laboratory of Dr. Tarun Kapoor at the Rockefeller University. In addition to the NIH New Innovator Award, Radhika is a Pew Biomedical Scholar and a recipient of the Smith Family Award for Excellence in Biomedical Research.

Brian Wainger, M.D., Ph.D.
Massachusetts General Hospital | Harvard Medical School

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“I’m thrilled to receive the award. It’s a great honor, and I’m grateful for the hard work of my group, particularly Joao Pereira and Anna-Claire Devlin, that enabled it. It’s also of course due to very strong support from MGH, the departments of Neurology and Anesthesia, Critical Care & Pain Medicine. And with the award comes an even greater responsibility to produce research that ultimately helps our patients – I’m excited and humbled by that.”

Project Title: A Human Stem Cell-Derived Neuromuscular Junction Model for Amyotrophic Lateral Sclerosis
Grant ID: DP2-NS-106664

Brian Wainger is a physician scientist at Massachusetts General Hospital and Assistant Professor of Neurology and Anesthesiology at Harvard Medical School. He received his undergraduate degree in molecular biology from Princeton University and M.D./Ph.D. degrees from Columbia University, where he worked on ion channel physiology with Steven Siegelbaum. Following medical residency in the Partners Neurology Program and clinical fellowship in Interventional Pain Medicine at Massachusetts General Hospital, he completed a research fellowship with Clifford Woolf at Boston Children’s Hospital and the Masters Program in Clinical and Translational Investigation at Harvard Medical School. He is a Principal Investigator at Massachusetts General Hospital, Principal Faculty at the Harvard Stem Cell Institute and a member of the Harvard Neurobiology Program. His lab research focuses on modeling motor and sensory neuron diseases using stem cell technology and electrophysiology.

Early Independence Award

The Early Independence Award supports outstanding junior scientists with the intellect, scientific creativity, drive, and maturity to flourish independently by bypassing the traditional post-doctoral training period.

Zirui Song, M.D., Ph.D.
Harvard Medical School and Massachusetts General Hospital

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“It is an honor to receive this grant and join an inspiring community of investigators. I am grateful to the faculty and colleagues who made my training possible. This grant will allow me to continue my research on strategies to improve the value of care, including studying efforts to decrease costs, improve quality, and increase the sustainability of our public programs like Medicare. In addition, this grant provides an opportunity to better understand how providers are leading delivery system reforms on the front lines and how different segments of the population are faring in the era of health care reform.”

Project Title: Inequities in Health Outcomes in the Twenty-First Century: Understanding New Causes and the Impact of Delivery System Reforms on Health Care Disparities
Grant ID: DP5-OD-024564
Funded by the National Center for Complementary and Integrative Health

Zirui Song is an assistant professor of health care policy at Harvard Medical School and an internal medicine physician at Massachusetts General Hospital. His research has focused on health care spending and quality under new payment models for provider organizations, the impact of changes in Medicare physician payment policy, and the economics of health insurance in the Medicare Advantage program. He received a B.A. in Public Health Studies with honors from Johns Hopkins University, an M.D. magna cum laude from Harvard Medical School, and a Ph.D. in Health Policy, Economics track, from Harvard University, where he was a fellow in Aging and Health Economics at the National Bureau of Economic Research. He completed his residency training at Massachusetts General Hospital.