12 Days of Research at Mass General: A Strategy for Sneaking Drugs Into Tumor Cells

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.

July 2017:

Could a Technique Echoing an Ancient Greek Military Strategy Point the Way to More Effective Cancer Treatments?

Trojan horse

According to Greek legend, the Trojan horse was a wooden structure built by Greek soldiers and presented to the Trojans as a gift after a long and fruitless siege of the city during the Trojan War. When the Trojans brought the gift horse within their city walls, the Greek soldiers who were hidden inside crept out under the cover of night and launched a deadly surprise attack. Historians continue to debate how much of the tale is based in fact and how much in myth.

At Massachusetts General Hospital, a real-life Trojan horse scenario that takes place on the nanoscale level could provide a way to sneak cancer drugs into fortified tumor cells so the drugs can attack from within.

Here are five things to know about a new study from the Mass General Center for Systems Biology:

1. Think of nanoparticles as the Trojan horses of cancer therapy. These tiny molecules (typically between 20 and 100 nanometers in size) are increasingly being used to transport drugs to a specific target in the body. The ability that researchers have to easily change the size and surface characteristics of the nanoparticles and control the time and location of the drug’s release makes them ideal for drug delivery systems.

2. Nanoparticles are small enough to carry the drugs (the Greek soldiers) through the body and can protect the encapsulated drug from toxic substances in the bloodstream that are used in infusion chemotherapy. However, in clinical practice, getting these nanoencapsulated drugs into patients’ tumors has been challenging—tumor blood vessels are difficult to break through, which limits the passage of any drugs from the bloodstream into tumor cells. Although it’s usually beneficial for blood vessels to maintain barrier function, their tough exteriors are a disadvantage in cancer therapies.

3. A 2015 study by Miles Miller, PhD, of the Center for Systems Biology, and his colleagues showed that tumor-associated macrophages — immune cells found around tumors that are in charge of engulfing pathogens, foreign materials and dead cells — can improve delivery of nanoparticle-based therapies to tumor cells. They also found that radiation therapy made it easier for substances to pass through tumor blood vessels. But exactly how these effects are produced and how they could be combined to enhance nanomedicine delivery was not known. Answering those questions was the goal of the current study.

4. Miller and his team found that macrophages can be prompted to act like Trojans, helping to bring the drugs inside the tumor, if the tumors are treated with radiation prior to administering the drugs. In the same way that a siege weakens the resistance of a city, the radiation weakens the blood vessels within the tumor. It also increases the number of macrophages attracted to tumor blood vessels which, in turn, pick up the drug-laden nanoparticles and bring them into the tumor. The sudden influx of macrophages into the weakened walls of the blood vessels causes many of the vessels to burst, thus flooding the tumor cells with the drug-laden nanoparticles and improving drug delivery by 600 percent.

5. “Finding that this combination of radiation and nanomedicine leads to synergistic tumor eradication in the laboratory provides motivation for clinical trials that combine tumor rewiring using radiation therapy with nanomedicine,” says Miller, who was lead author of the study. “Most of the treatments and nanomedicines employed in this study are FDA approved for cancer treatment, so this combination treatment strategy could be tested in clinical trials relatively quickly.”

Radiation & Macrophages

Ralph Weissleder, MD, PhD, Director of the MGH Center for Systems Biology is senior author of the Science Translational Medicine paper.

You can find the original post here.

12 Days of Research (10)

12 Days of Research at Mass General: Aspirin and Risk of Cancer Death

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.

April 2017:

New Study Finds Low-Dose Aspirin May Lower Risk of Cancer Death

63889039 - heap of round white tablets and plastic pills bottlenew study from Massachusetts General Hospital reports that long-term regular aspirin was associated with a lower risk of dying from various types of cancers.

Lead author, Yin Cao, MPH, ScD, a researcher in the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital, and her team studied the health outcomes of approximately 86,000 women and 44,000 men who had been prescribed aspirin at various doses and duration over the course of 32 years.

The biggest benefit came from reducing colorectal cancer deaths: Men and women who regularly took aspirin reduced their chances of dying from colorectal cancer by a third. Women also reduced their risk of dying from breast cancer by 11 percent, while men were 23 percent less likely to die from prostate cancer. The benefit seemed to be greatest for people taking two to seven doses of regular-strength aspirin—325 mg per tablet—each week.

It’s still not entirely clear how aspirin lowers cancer risk. Researchers suspect that aspirin’s ability to lower inflammation and control inflammatory factors that may contribute to abnormal cell growth in tumors may reduce risk. Plus, its anticoagulant properties that prevent clots from forming may prevent cancerous cells that break away from tumors from sticking to other areas in the body and growing into metastatic tumors.

Regular aspirin use has already been recommended as a preventative measure against cardiovascular disease and colorectal cancer.

Cao cautions that patients and physicians should consider all potential benefits and risks before beginning any new aspirin regimens. More work is needed to weigh these potential benefits against the risks of long-term use, which include gastrointestinal bleeding and hemorrhagic stroke.

The data of this study was presented at the American Association for Cancer Research Annual Meeting 2017, which took place earlier this month in Washington, DC.

You can find the original post here.

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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:

Crowdsourcing Cancer Research – Researchers at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital will be recruiting attendees at the annual Radiological Society of North America meeting next week to help them label tumors from an archive of images from the Cancer Imaging Archive. Once the tumors are identified, the images will help create new machine-learning based tool cancer diagnoses and prognosis.

Looking Back: Mass General and the Coconut Grove Fire – This Proto podcast talks about the role Mass General played in treating victims of the deadly Cocoanut Grove fire in Boston in 1942, in which 492 people died. The podcast features the story of a survivor who was treated at Mass General and an interview with surgeon John Schulz on how the fire led to innovations in burn care.

Study finds that 1 in 5 show symptoms of PTSD after cancer diagnosis – Roughly 1 in 5 cancer patients developed post-traumatic stress disorder within six months of their diagnosis—and a small percentage still experienced trauma-related symptoms six months later, according to new research in the journal Cancer. The study was conducted by a research team that included investigators from Boston (the Dana Farber Cancer Institute) and Malaysia.

Science in the House: A Live DJ/VJ experience inspired by particle physics – Check out highlights of a two performances from the Manchester Science Festival that combine electronic dance music with science themed visuals.

Top photo courtesy of the Martinos Center for Biomedical Imaging

Researchers Use Machine Learning to Improve Breast Cancer Screening Techniques

Imagine enduring a painful, expensive and scar-inducing surgery—only to find out afterwards that it wasn’t necessary.

This is the situation for many women with high-risk breast lesions—areas of tissue that appear suspicious on a mammogram and have abnormal but not cancerous cells when tested by needle biopsy. Following surgical removal, 90% of these lesions end up being benign.

A change in the standard of care could be on the horizon thanks to researchers at Massachusetts General Hospital and MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) who have found a more precise and less invasive way to separate harmful lesions from benign ones.

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From left: Manisha Bahl, director of the Massachusetts General Hospital Breast Imaging Fellowship Program; MIT Professor Regina Barzilay; and Constance Lehman, chief of the Breast Imaging Division at MGH’s Department of Radiology. Photo courtesy of MIT News

“The decision about whether or not to proceed to surgery is challenging, and the tendency is to aggressively treat these lesions [and remove them],” said Manisha Bahl, MD, Director of the Breast Imaging Fellowship Program at Mass General, in a recent interview.

Bahl, along with a team of researchers, have harnessed the power of artificial intelligence (AI) to develop a more accurate and less invasive screening method for high-risk lesions. When tested, the machine correctly diagnosed 97 percent of 335 high-risk breast lesions as malignant and reduced the number of benign surgeries by more than 30 percent compared to existing approaches. These results were recently published in Radiology.

The team developed an AI system that uses machine learning to distinguish between high-risk lesions that need to be surgically removed from those that should just be watched over time. They created this model by feeding it data on over 600 high-risk lesions, including information on the patient’s demographics and pathology reports, and then tasked it to identify patterns among the different data elements.

Through a process called deep learning, the machine uses the data to create an algorithm that can be used to predict which high-risk lesions should be surgically removed. This process differs from traditional software programming in that the researchers did not give the machine the formula for diagnosis, but rather let it analyze the data and identify patterns on its own.

“To our knowledge, this is the first study to apply machine learning to the task of distinguishing high-risk lesions that need surgery from those that don’t,” said collaborator Constance Lehman, MD, PhD, chief of the Breast Imaging Division at Mass General’s Department of Radiology, in a recent interview. “We believe this could support women to make more informed decisions about their treatment and that we could provide more targeted approaches to health care in general.”

Lehman says Mass General radiologists will begin incorporating the model into their clinical practice over the next year.

Could the Microbiome be the Key to Ending Chemotherapy-Induced Pain?

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Most of us have experienced the odd sensation of “pins and needles” in our hands or feet. While annoying and painful, the sensation usually goes away quickly.

But for many people with peripheral neuropathy, a disorder involving increased sensitivity of nerves outside of the brain and spinal cord, this experience may linger for months to years.

“It’s a horrible condition,” said Shiqian Shen, MD, clinical investigator in the Massachusetts General Hospital Center for Translational Pain Research and director of the Mass General TelePain Program. “You literally want to shake off your leg, but you can’t.”

Unfortunately, a third of cancer patients who receive chemotherapy encounter this as a side effect, a condition known as chemotherapy-induced peripheral neuropathy (CIPN). This neuropathy is a result of nerve damage or impairment of the nervous system and often is chronic. If the pain is severe enough, chemotherapy dosages must be lowered, which causes the treatment to be less effective.

With the survival rates for many cancers increasing due to the improved understanding of genetic mutations, targeted therapies and immunotherapy, CIPN has become a major challenge and can hurt a survivor’s quality of life.

Dr. Shen and Jianren Mao, MD, PhD, chief of the Mass General Pain Management Center and vice chair for research in the Department of Anesthesia, Critical Care and Pain Medicine, are leading a research team in exploring why patients undergoing chemotherapy develop CIPN.

There is strong evidence that the gut, which carries about 10 trillion bacteria, has a major impact on the central nervous system. Previous research in the field has also shown that gut microbiota plays a critical role in the tumor-killing effect of many chemotherapeutics drugs. In a recent study published in Nature Neuroscience, the researchers questioned whether an immune response that results from interactions between chemotherapy drugs and the bacteria in the microbiome also plays a role in developing CIPN.

The researchers exposed two sets of mice, one with a normal microbiome and one that had their microbiome essentially eliminated through antibiotic treatments or genetic engineering, to oxaliplatin—a chemotherapy drug used to treat colon or rectal cancer and that is known to cause CIPN. The normal mice manifested symptoms of CIPN while those without a microbiome did not. Therefore, a microbiome is necessary for CIPN symptoms to manifest.

Next, the team dug into why the microbiome influences the onset of CIPN.

The researchers determined that the mice who experienced CIPN had higher levels of two proteins involved in inflammation (IL-6 and TNFalpha) in the dorsal root ganglia (DRG). This inflammatory response in the DRG leads to an increase in neuron sensitivity, which is what causes the neuropathy pain and tingling in a person’s extremities.

The team found further evidence that suggests a reaction between the chemotherapy agent and bacteria in the microbiome, releases lipopolysaccharides (LPS), a molecule found in bacteria on the gut lining, into the bloodstream. LPS then appears to cause a chain reaction that increases the levels of the two inflammatory proteins in the DRG.

“We found there’s a concurrent response—one initiated by the chemotherapy agent, and one by the inflammatory response,” said Shen. “They work hand in hand to promote the pain.”

However, there is a dilemma to sort out. Previous research has found that chemotherapy treatments such as oxaliplatin and cyclophosphamide are dependent on the gut microbiome. Meaning chemotherapy does not work well without help from a normal microbiome, but having it runs the risk of developing CIPN.

“Our research has revealed that you cannot get rid of the gut microbiome entirely to prevent side-effects because your therapeutic effect is also linked to the same presence,” says Shen.

The researchers are conducting follow-up studies to see if the same results are found in humans, and to see whether the same phenomenon exists in other type of neuropathic pain.

Potential in the Clinic

Since eliminating a cancer patient’s microbiome will essentially render chemotherapy treatment ineffective, more research will need to be done to see if investigators can determine if and how an individual’s microbiome composition affects their likelihood of developing CIPN. If they can identify favorable bacteria profiles, clinicians may be able to reduce the risk of developing CIPN by prescribing probiotics or fecal transplants in advance of starting chemotherapy. On the flipside, knowing the optimal microbiome profile that reduces risk of CIPN for every chemotherapy agent may help oncologists select the ideal chemotherapy drug for each patient.

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:

Creative Minds: A New Way to Look at Cancer

Better Patient-Provider Communication Needed for Obesity Care

Eugenics 2.0: We’re at the Dawn of Choosing Embryos by Health, Height, and More

6 Speaking Tips for Scientists and Engineers (editor’s note: Melissa Marshall, featured in this article, recently spoke to Mass General clinicians about how to effectively present scientific work. We were so impressed by her talk that we wanted to introduce her to our readers) 

Looking for a great book for the young scientist in your life? The long list of 2018 AAAS/Subaru SB&F (Science Books and Films) Prize winners for Excellence in Science Books has been released. Prizes are awarded each year in the following categories:

  • Children’s Science Picture Books
  • Middle Grade Science Books
  • Young Adult Science Books
  • Hands on Science Books

See the full list here

 

Top photo: courtesy of Tim Lahan, MIT Technology Review

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.”

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.”

Meet a Mass General Postdoc: Echoe Bouta

In honor of National Postdoc Appreciation Week, all this week we’ll be sharing profiles of just a few of our amazing Mass General postdocs to highlight their research and what inspires them.

Meet Echoe Bouta, PhD, a research fellow in the Department of Radiation Oncology.

Postdoc week Bouta (1)

Where did you get your PhD from?

University of Rochester

What questions are you asking in your current research? What do you hope to find out?

Lipedema is a chronic disorder that results in increased fat in the lower limbs and manifests as dramatic, painful swelling. Clinical studies demonstrate that patients present with at least partial lymphatic dysfunction, which worsens until lymphedema occurs. As the etiology is largely unknown, treatments are often ineffective, demonstrating the need to understand the relationship between fat and lymphatic capability.  The questions I hope to answer are:

      •  How does increased adiposity impair lymphatic function in an animal model of obesity?
      • Can we target key pathways in this process to improve lymphatic function?

The answer to this questions will hopefully catalyze new treatments for lipedema.

What drew you to this field?

The lymphatic research field is relatively young compared to other research fields.  I believe that we have only started to discover the importance of the lymphatic system in multiple disease states and it is exciting to be part of that.

What is a typical day like for you?

Much of my project involves imaging of the lymphatic system under different contexts, such as obesity or after delivery of a drug. Therefore, a typical day for me is a mix of in vivo experiments, data analysis and writing.

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

The people.  We are surrounded by talented scientists from a variety of fields that results in a very interdisciplinary research environment.

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.