Study Identifies New Targets for Huntington’s Disease Research

Ghazaleh Sadri-Vakili, PhD, is the director of the NeuroEpigenetics Laboratory at Massachusetts General Hospital’s Institute for Neurodegenerative Diseases (MIND).  Her work investigating the genetics of Huntington’s disease was recently featured in an article on the Mass General Giving website.

Here are five things to know:

  1. Huntington’s disease (HD) is a fatal genetic disorder that causes the progressive breakdown of nerve cells in the brain. Symptoms typically start occurring between the ages of 30 and 50. The disease is highly heritable—each child of a parent with HD has a 50% chance of inheriting the faulty gene.
  2. According to the Huntington’s Disease Society of America (HDSA), symptoms of HD typically begin with a loss of coordination and cognitive skills. These declines get more pronounced as the disease progresses. In late stages, HD patients lose the ability to walk and speak, and choking becomes a major concern. Death is typically due to complications from the disease and not the disease itself.
  3. Researchers at Massachusetts General Hospital have been at the forefront of research into the genetic underpinnings of Huntington’s disease for the past two decades. In 1983, a team led by James Gusella, PhD, identified the section on chromosome 4 where the HD gene was located. In 1993, a multi-institutional research group that included Marcy E. MacDonald, PhD, and Dr. Gusella identified the gene itself.
  4. Recently, a research team led by Ghazaleh Sadri-Vakili, PhD, has been studying how gene expression differs in patients with HD. Her team has identified two ways in which a genetic pathway known as the Hippo pathway malfunctions in HD. These malfunctions cause HD patients to produce too much of an enzyme called MST, and not enough of a protein called YAP.
  5. If researchers are able to identify drugs that correct this imbalance, they may be able to develop treatments that slow or halt the progression of the disease.

Celebrity Patients Bring Lupus into The Headlines, But Much Remains Unknown

This September, actress and singer Selena Gomez announced on Instagram that she underwent a kidney transplant as part of her treatment for lupus, an autoimmune disease in which a body’s immune system begins to attack its own tissues and organs.

Gomez and other celebrities such as Nick Cannon, Toni Braxton and Seal have publicly spoken out about their struggles with lupus, which affects 1.5 million Americans and over five million people worldwide. Despite these high-profile patients, the disease still remains a mystery to much of the general public and the scientific community.

To shed light on symptoms, causes and treatment options for the disease, April Jorge, MD, a research fellow in the rheumatology unit at Massachusetts General Hospital , recently gave a talk on “Understanding the Mystery of Lupus” at Mass General’s Maxwell and Eleanor Blum Patient and Family Learning Center.

What is Lupus and Who Does it Affect?

The immune system typically protects us against infections by forming antibodies that detect and respond to invading pathogens, such as viruses and harmful bacteria. However, Jorge explained that in patients with lupus, the body forms auto-antibodies that target the own body’s cells as if they were intruders.

Lupus is a non-contagious and non-infectious disease that is caused by a combination of environmental and genetic factors. Jorge said that at least 50 different genes contribute to an increased risk of developing the disease.

Lupus is more common in women, and in African Americans and Hispanic populations. Patients are typically diagnosed between the ages of 15 to 45 years.

Symptoms of Lupus

Symptoms of lupus include skin rashes, hair loss, sores in the mouth, foggy thinking, seizures, vision problems, joint pain, liver inflammation, inflammation in the lining of the lungs and heart, blood clots, fatigue, and fever, among others.

“People with lupus also have a higher risk of heart attacks and strokes, and can be at a greater risk of getting osteoporosis and depression,” said Jorge. Lupus can also damage internal organs, especially the kidneys. Up to 50 percent of patients with lupus develop lupus nephritis—an inflammation of the kidneys that can prevent them from functioning properly.

Jorge suggested patients look out for several symptoms that may be warning signs of kidney damage.

“There can be some signs like swelling in the legs or belly,” she said. “Sometimes, it’s picked up by doctors if the patient has high blood pressure.” Other lupus patients may not have any outward symptoms of kidney damage, which makes it important for them to undergo regular screenings.

Diagnosis

Jorge explained that the disease is so complex because signs and symptoms differ from person to person. Many times, symptoms of lupus overlap with those of other disorders. Hence, it takes an average of 6 years to obtain a lupus diagnosis.

Diagnosis is typically made by factoring in combination of symptoms, blood tests and other factors, such as impaired liver or kidney function as a result of inflammation.

Treatment

While there is no cure for lupus, it is possible to treat the symptoms with medications and lifestyle changes.

Pharmaceutical Options

Medications prescribed for treating lupus include Prednisone (a corticosteroid that acts as an immune suppressant), Hydroxychloroquine (a drug originally used to treat malaria) and other immunosuppressant medications.

Currently doctors and scientists are trying to identify new and more effective treatments for lupus with fewer side effects. Jorge is optimistic about new drugs on the horizon that could improve treatment options. She said that biologics (products derived from natural—rather than chemical—sources) target certain parts of the immune system and are some of the most effective medications for lupus.

“Belimumab (manufactured under the brand name Benlysta®), which is given either as an injection or through an IV infusion, is the first drug to be approved for lupus in 50 years,” said Jorge. “But in the next five to 10 years, there will be many more.”

Lifestyle Modifications

Lifestyle changes can also help manage the symptoms of lupus, such as:

  • Exercising regularly
  • Getting enough sleep
  • Eating a healthy diet with fruits, vegetables and lean meats
  • Avoiding excess sun exposure
  • Using sunscreen lotions with at least SPF 50 and wearing protective clothing
  • Avoiding tobacco, as studies have indicated that smoking can make the disease more severe and harder to control

Based on recent research findings, the same strict guidelines may not apply to alcohol consumption. Jorge is currently investigating the impact of alcohol use on risk of heart attacks and death in patients with lupus. The research team has found that patients with lupus who consume light to moderate alcohol intake have lower rates of heart attacks and overall mortality than those who do not consume any alcohol.

To learn more about Lupus, please visit the Lupus Foundation of America’s website.

Weekend Links

AP131960397-1024x576.jpg

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

A New Study Finds Good News About Treating Addiction – Dr. John Kelly of the Recovery Research Institute at Massachusetts General Hospital talks about his new study and says there’s some good news when it comes to treating addiction.

‘Null’ Research Findings Aren’t Empty of Meaning. Let’s Publish Them – op-ed written by Mass General investigator and physician Anupam Jena, MD, PhD.

The Secret to Long Life? It May Lurk in the DNA of the Oldest Among Us

15 Really Good Things Happening in Science Right Now

How to Write Science Stories (Volume 1: Story Structure) 

Up-Goer Five Challenge: Explain Your Research Using the Ten Hundred Most Common Words

(top photo courtesy of STAT) 

Investigators Add New Insights to Lyme Disease Diagnosis and Treatment

tick.jpgWith the number of reported Lyme disease infections expected to reach record highs in 2017, Massachusetts General Hospital researchers are helping to meet the need for new diagnostic tools and treatments.

The work of John Branda, MD, and Allen Steele, MD, was recently featured on the Mass General Giving Website. Here is a brief summary of the article, which you can find in full here.

A New Test for Lyme Disease

Lyme disease is caused by the bacterium Borrelia burgdorferi (B. burgdorferi), which is transmitted to humans through the bite of an infected blacklegged tick, commonly known as a deer tick. The tick must be attached for 36 to 48 hours or more before the Lyme disease bacterium can be transmitted.

As with many infectious diseases, early detection plays a key role in treatment. John Branda, MD, associate director of the Clinical Microbiology Laboratory at Mass General, and his colleagues are developing a new way to diagnose Lyme disease, as current blood tests frequently yield false negative results in the weeks after infection.

The team’s new testing technique starts with a blood sample that is first amplified by polymerase chain reaction technology, a method that can make the genetic material of a pathogen such as B. burgdorferi more easily identifiable.

Then the blood is then scanned with magnetic resonance imaging, which can quickly pick up the Borrelia DNA. The test, known as T2MR, was able to detect B. burgdorferi in blood samples from patients who were suspected of having Lyme disease but had tested negative using traditional techniques.

Genetic Factors

In a separate research study, Allen Steere, MD, a Mass General rheumatologist and the researcher who led the team that first identified Lyme disease in the 1970s, is exploring why some patients do not recover from the disease even after receiving a course of antibiotics.

While the antibiotics are able to clear the infection, some patients still experience pain, fatigue and neurocognitive symptoms. A few patients can go on to suffer from antibiotic-refractory Lyme arthritis — a painful inflammation of the joints that long outlasts the infection.

In these patients, there is mounting evidence that Lyme disease triggers an abnormal immune response, which in turn attacks the tissues of the joints, even after B. burgdorferi has been cleared by antibiotics.

Dr. Steere believes that many more severe cases may result when people with a specific genetic profile encounter a particularly virulent strain of the bacterium.

When genetic susceptibility and virulent B. burgdorferi strains combine, as they do in as many as 20% of people of Caucasian ancestry who are infected with Lyme disease, ideal conditions are created for an amplified and maladaptive inflammatory response that can attack joint tissues.

To learn more about the symptoms and causes of Lyme disease, and for tips on protecting yourself from tick bites, please visit the Centers for Disease Control’s Lyme disease website.

A Snapshot of Science at Mass General: A New Approach to Targeted Cancer Treatments, Identifying Genes that Help Protect the Gut and Much More!

We wanted to share some recent Massachusetts General Hospital 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 on the Mass General website!


Cognitive Decline, Tau and β-Amyloid in Healthy Older Adults
(Summary submitted by Rachel Buckley, PhD, and Rebecca Amariglio, PhD, both of the Martinos Center for Biomedical Imaging)

We published findings from the Harvard Aging Brain Study (Department of Neurology, Massachusetts General Hospital) investigating the link between subjective memory complaints (when a patient reports a worsening of their thinking abilities, including memory) and Alzheimer’s disease pathology in individuals who are otherwise cognitively normal. We found that increasing memory complaints were linked with greater amounts of tau in the brain, a naturally occurring protein that is associated with neuron loss in Alzheimer’s disease. We posit that memory complaints are a very early marker of disease, as they relate to tau build up before clinical tests can detect memory impairment.

Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, [et al.] Amariglio RE
Published in JAMA Neurology on October 2, 2017


New Approach to Targeted Cancer Treatment 
(Summary submitted by Conor L. Evans, PhD, of the Wellman Center for Photomedicine)

We have created a promising new light-activated, cancer-targeting therapeutic. Cancer drugs often cannot reach every cell in a tumor, leaving behind cells that can become resistant to treatment. At the same time, these drugs can cause unwanted systemic problems, such as weight and hair loss, elsewhere in the patient’s body. Our therapeutic was built to diffuse throughout tumors, target cancer cells, and kill these cells only when activated by light to avoid unwanted and burdensome side effects. We hope that this approach could one day find use in the fight against treatment-resistant cancers, like breast and lung.

An Integrin-Targeted, Highly Diffusive Construct for Photodynamic Therapy
Klein OJ, Yuan H, Nowell NH, Kaittanis C, Josephson L, Evans CL
Published in Scientific Reports on October 17, 2017


Identifying Genes that Help Protect the Gut 
(Summary submitted by Javier Elbio Irazoqui, PhD, formerly of the Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease)

The intestinal epithelium is a single layer of cells that protects the gut from environmental insult. Defects in this layer are linked to many diseases, including inflammatory bowel disease. Despite its critical importance, very little is known about the genes in the epithelium involved in this function. We found that transcription factor TFEB, a master regulator of lysosomal gene expression, provides a protective effect, and this function is mediated by expression of apolipoprotein A1, the major constituent of HDL, aka “good” cholesterol. Our findings suggest that enhancement of TFEB activity in the intestinal epithelium could be a therapeutic approach to enhance Apolipoprotein A1 expression for the treatment of inflammatory bowel disease.

Transcription Factor TFEB Cell-Autonomously Modulates Susceptibility to Intestinal Epithelial Cell Injury In Vivo
Murano T, Najibi M, Paulus GLC, Adiliaghdam F, Valencia-Guerrero A, Selig M, [et al.] Xavier RJ, Lassen KG, Irazoqui JE
Published in Scientific Reports on October 24, 2017


Patient Resistance to Immune Checkpoint Blockade Therapies
(Summary submitted by Nir Hacohen, PhD, of the Cancer Center)

Cancer therapy has been transformed in the last few years by immune-based therapies, called ‘checkpoint blockade’ therapies. An important question is why some people respond and others do not respond to this therapy. By analyzing the DNA of tumors from patients who developed resistance to checkpoint therapy, we found changes in the DNA of a key gene that is critical for tumors to be detected by the immune system. In this way, the tumor has learned how to hide from the immunotherapy. Knowing this will help us decide which patients would benefit from immune therapy. Finding ways to make these resistant tumors visible to the immune system is an important goal for the coming years.

Resistance to Checkpoint Blockade Therapy Through Inactivation of Antigen Presentation
Sade-Feldman M, Jiao YJ, Chen JH, Rooney MS, Barzily-Rokni M, Eliane JP, [et al.] Flaherty KT, Sullivan RJ, Hacohen N
Published in Nature Communications on October 26, 2017

World Diabetes Day 2017: Recent Diabetes Research from Massachusetts General Hospital

tumblr_inline_ofnq35sy4J1tq32mi_540.jpgDiabetes impacts an estimated 425 million people around the world, and that number is projected to rise to 693 million by 2045, according to the annual diabetes atlas released today by the International Diabetes Federation (IDF).

Diabetes develops as a result of having too much sugar in the blood. Over time, that imbalance can cause serious and costly health problems including heart disease, stroke, kidney disease and eye problems. The IDF diabetes atlas estimates that the world spends more than $720 billion on health care expenditures related to the disease.

November 14 marks World Diabetes Day – a day to raise awareness of the growing diabetes epidemic and the need for a cure as well as improved prevention and treatment methods.

Here are just a few examples of how Massachusetts General Hospital researchers are working to advance diabetes research and care:

  • Investigators have reason to believe that a vaccine originally used to treat tuberculosis could provide new hope for patients with type 1 diabetes.
  • People with type 2 diabetes are particularly prone to ulcers on the bottom of the foot, which can increase the risk of death and often result in a major amputation. Ulcers take months to heal, but a new discovery about mature B lymphocytes – best known for producing antibodies – could hasten wound recovery.
  • Researchers have developed a new method for measuring blood sugar levels in diabetes patients that could reduce testing errors by 50 percent.
  • Treatment guidelines for patients with type 1 diabetes have long called for yearly eye exams. But is there an alternative to this one-size-fits-all approach that could reduce patient burden and costs while providing a quicker diagnosis? Findings from a recent study lend insight into a possible new eye screening protocol.
  • Check out the Mass General Diabetes Unit, which seeks to advance the care of people with diabetes nearby and worldwide. U.S. News & World Report ranks Mass General Diabetes & Endocrinology among the best in the nation.

 

Weekend Links

Placebo.png

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

Rebranding placebos: Harnessing the power of sham therapies for real healing might require a new lexicon

Researchers produce the first draft cell atlas of the small intestine

‘Extraordinary’ tale: Stem cells heal a young boy’s lethal skin disease

Decisions, Decisions: The Neuroscience of How We Choose (Science Weekly podcast)

Are you preparing a research poster?
A Quick Poster Checklist (From the University of Washington)
University of Texas Poster Review

Top photo courtesy of Knowable Magazine (CREDIT: TEXTBOOK EXAMPLE [CC BY-ND])

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.

MIT-AI-Cancer-Detection-01_0.jpg
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.

Pocket-Sized Device Provides Food Allergy Sufferers with Life-Saving Tableside Lab Results

If you’re among the 50 million Americans with a severe allergy to foods like gluten or nuts, every meal at a restaurant can feel like a potential land mine. Even if the restaurant has made an effort to provide dishes that are allergen-free, worries of cross-contamination and a subsequent severe or potentially life threatening reaction can still put a damper on your dinner plans.

To help ease concerns and keep food allergy sufferers safe, a team of researchers at Massachusetts General Hospital has developed a new device small enough to fit on a keyring that costs only $40 and can quickly and accurately test for food allergens.

While advances have been made in the packaged food industry, where new federal regulations require the manufacturer to disclose whether the product is made in a facility that also processes common allergens, these disclosures are not always accurate and there are no similar regulations for the restaurant industry.

Rather than force diners to completely avoid foods that have the chance of containing an allergen, or eat something only to regret it later, Mass General researchers created integrated exogenous antigen testing (iEAT), a pocket-sized device that can accurately analyze food for the presences of allergens in less than 10 minutes. Specifically, the device can screen for peanuts, hazelnuts, wheat, milk and eggs.

keychain pic.jpeg
The iEAT system

Developed by co-senior team leaders Ralph Weissleder, MD, PhD, Director of the Center for Systems Biology (CSB) at Mass General and Hakho Lee, PhD, Hostetter MGH Research Scholar and Director of the Biomedical Engineering Program at the CSB, the device consists of three components:

  1. A small plastic test tube that the user can put a small sample of food into. The tube contains a solution that dissolves the sample and adds magnetic beads to the solution. The beads are designed to bind to the food allergen of interest.
  2. The user can then drop the solution onto an electrode chip, which is inserted into the keychain sized reader.
  3. The reader analyzes the sample and indicates on a small display whether the allergen is present, and if so, in what concentration.

Testing performed by the research team showed that measurements of the concentration of the allergen is extremely accurate. In fact, the device could detect levels of gluten that were 200 times lower than the federal standard. Accuracy is key because everyone’s sensitivity varies — some individuals could experience a reaction after consuming a miniscule trace of an allergen.

Weissleder and Lee have also developed a smartphone app to complement iEAT. With the app, users can compile and store the data they collect as they test different foods for various allergens at different restaurants and even in packaged foods. The app is set up to share this information online so others with the app will be able to find restaurants with foods that consistently have no or low levels that are below the individual’s triggering concentration.

cell phone app

Consumers may be able to purchase the $40 iEAT device and corresponding app in the near future — the research team has granted a license to a local start-up company to make the system commercially available. Weissleder and Lee also report that they could apply this technology to detect other substances in food such as MSG or even pesticides.

This research was recently highlighted in an NIH article and published in ACS Nano.

It was also recently featured in a news story on CBS Boston.

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

gut-microbiome.jpg

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.