AGA-Aman Armaan Ahmed Family Summer Undergraduate Research Fellowship (SURF)

Research: I lead a research program in the field of gastrointestinal (GI) epithelial cell and developmental biology. My lab uses cutting-edge organoid and animal models to delineate fundamental mechanisms involved in GI development, homeostasis, and disease. Our current projects focus on GATA transcription factors and their roles in normal GI development, metaplasia, and cancer. 

Project(s): An undergraduate student will participate in our studies of GATA4 function using human GI organoid models derived from normal, metaplastic, and malignant GI tissues. In addition to gaining experience in cutting edge organoid culture systems, the undergraduate will gain proficiency in molecular biology techniques including transcriptional profiling and chromatin immunoprecipitation.

Website: https://www.mcw.edu/departments/cell-biology-neurobiology-and-anatomy/people/michele-battle-phd

Research: As a physician-scientist I am interested in discovering the cells and molecules involved in normal gut motor and sensory function, and how they are disrupted in disease, such as irritable bowel syndrome. Current efforts in the lab are focused on a sensory pathway we call “gut touch,” because this sensory circuit is very similar to the skin touch circuit. We use a range of cutting-edge techniques in enteric neuroscience that range from examinations of single molecules to studies in animals and humans.

Our group is a part of the Mayo Clinic’s Enteric Neuroscience Program (ENSP), which has a long and distinguished history in the field, and is composed of several labs, so there are always many interesting collaborations and discussions.

Project(s): We have several projects ongoing that we will tailor to the students’ needs and interests. These include microscopy approaches, (immunofluorescence, super-resolution microscopy), in vitro studies looking at cell and tissue function by electrophysiology and calcium imaging, and in vivo studies that ask what the gut touch system’s role is in gut physiology.

Website: https://www.mayo.edu/research/labs/gastrointestinal-mechanotransduction

Research: COMMD proteins: We study the regulation of endosomal protein sorting and immune function by members of the COMMD protein family. Genetics of inflammatory disorders: Our lab also investigates the genetic basis of disorders of immune function, particularly affecting the gastrointestinal (GI) tract, mucosal immunity, and immune-tumor interactions in the GI tract.

Project(s): We are investigating how endocrine cells of the gut communicate with the intestinal microbiome to regulate metabolic control. The project involves both animal model experiments as well as large data set analysis, including microbiome sequencing interpretation. Given the impact of COVID on travel and in-person fellowships, the participating SURF trainee will be involved in computational analysis of microbiome data, presenting the data in lab meetings (which are happening remotely), and other large dataset analytic tools.

Website: https://profiles.utsouthwestern.edu/profile/30394/ezra-burstein.html

Research: My research is focused on the prevention of colorectal cancer using chemopreventive drugs and lifestyle interventions. I also lead research programs in the epidemiology of the gut microbiome, gastrointestinal bleeding, inflammatory bowel disease, gallstone disease, and COVID-19. I also have a laboratory that conducts translational research projects using a variety of human models, including intestinal organoids.

Project(s): If we are able to host students in person, the student can work in our laboratory conducting translational studies on human samples focused on chen-prevention of colorectal cancer with aspirin and other drug targets, as well as microbiome research. If entirely remote, the student will conduct analyses of epidemiological data related to colorectal cancer risk or COVID-19.

Website: https://www.dfhcc.harvard.edu/insider/member-detail/member/andrew-t-chan-md-mph/

Research: The role of serotonin transporter (SERT) as a therapeutic target for inflammatory bowel diseases and gut-brain disorders such as post traumatic stress disorder (PTSD).

Project(s): We have a novel transgenic inducible knock-in model of SERT that can lead to overexpression of SERT in neurons or epithelial cells. The project will aim to characterize this mouse model.

Website: http://chicago.medicine.uic.edu/departments/academic-departments/medicine/gastroenterology-and-hepatology/research/labs/gill-lab/

Research: The Hamilton lab studies epithelial cells in the gastrointestinal tract and the roles they play in maintaining human health. Epithelial cells form a barrier between the external environment and the rest of the body. While we understand a great deal about the function of gastrointestinal epithelial cells, there is still much to learn about how they behave during stress or disease states. We use in vivo and organoid models to identify new mechanisms directly relevant to regenerative medicine and inflammatory bowel disease.

Project(s): Project 1 (in-person, wet bench project): Defects in intestinal epithelial cells are a hallmark of disease in some children with inflammatory bowel disease (IBD). We are working with organoids derived from patients with IBD with epithelial defects to understand how the patients’ stem cells may behave differently than stem cells from individuals without IBD. The undergraduate student researcher will work directly with senior lab personnel to 1) learn to cultivate and analyze 3D organoid cultures, including cell culture sterile technique, live cell microscopy, data analysis and interpretation, and written/oral presentation and 2) learn about the clinical pathogenesis of inflammatory bowel disease, especially of the subtype being studied by the student in the laboratory.    Project 2 (remote project): The undergraduate student researcher will work together with our bioinformatician to analyze RNA sequencing data to compare pediatric healthy control patients to patients with inflammatory bowel disease. We have already completed and have sequencing data for n=30 patients per group and matching organoids from each patient. The project requires guided reading and discussion/presentation of relevant primary literature, weekly/bi-weekly virtual meetings with the PI and bioinformatician, figure generation, and development of the data into a manuscript including writing text for the first draft of the manuscript (with assistance from the PI and senior lab staff).

Skills wanted (not all are required):

1. Biology background with ability to read/synthesize primary literature in biomedical research
2. Interest in bioinformatics for Project 2 only
3. Strong oral/written communication
4. Independent learning and desire to take leadership in the project

Website: http://www.hamiltonlaboratory.org/

Research: My research, funded by NIDDK, studies the role of the microfilament in regulating epithelial homeostasis. We have identified intestinal epithelial cell actin binding proteins as cellular stress sensors and demonstrated that dysregulation of the cellular stress signaling contributes to the pathogenesis of Crohn’s disease. Other studies in the laboratory study the function of the actin bundling protein fascin in the pathogenesis to metastatic colorectal carcinomas. Fascin is not expressed in the normal adult epithleium but its expression is upregulated in most carcinomas, including aggressive metastatic colorectal carcinomas. Fascin expression in carcinomas is always linked to increased mortality and metastatic disease. The laboratory is identifying the molecular basis for fascin’s function in metastatic colorectal carcinomas.

Project(s): Students could work with colorectal cancer cell lines to monitor changes in fascin-expressing or fascin-null cells using confocal microscopy. The student could learn to use mouse models of colorectal carcinomas. Alternatively, the student could learn how to culture, maintain and study ex vivo cultures of mouse and human enteroids/colonoids.

Research: My research group focuses on gut sensation and motility disorders which are common medical problems that include gastroesophageal reflux disease, stomach pain, chronic nausea and vomiting, gastroparesis, irritable bowel syndrome, constipation, cyclic vomiting syndrome and eating disorders. We strive to understand what the connections are between the brain and the gut that cause symptoms and how to cope with them. We also study gut physiology to understand what affects how the gut moves things from one place to the other, whether it be too slow or too fast. We have projects trying to understand the impact of these diseases in underserved communities. As a result, we work on the gut microbiome and metabolites, human physiology experiments with devices and MRI, database analysis/epidemiology/healthcare services research studies, and clinical trials.

Project(s): We have several faculty members as well as research coordinators and many trainees who would work as a team with the student. The research work for this program would be clinical/translational with patient data including data acquisition and clean up as well as analysis under our guidance. The goal would be to actively engage in the clinical research project with a topic and would hopefully lead to presentation of results and involvement in publications. We also have a specialized clinic taking care of patients which will provide opportunities to shadow and appreciate the challenges with these medical issues.

Website: https://www.massgeneral.org/neurointestinal-health-center/

Research: My research focus is on functional bowel disorders such as irritable bowel syndrome (IBS), chronic constipation, and GERD. The IBS & Motility Center at Beth Israel Deaconess Medical Center is focused on advancing knowledge on the pathophysiology and treatment of functional gastrointestinal (FGID) and motility disorders. In addition to conducting research studies looking at the biological causes and psychosocial components of FGIDs and motility disorders, we are committed to investigating new potential treatments. Our clinical research team focuses on GI motility and functional bowel disorders. Our clinical research includes trials with a focus on alternative treatments (e.g., probiotics, placebo, vibrating capsule, etc.) and database analyses (e.g., evaluating predictors of improvement in symptoms).

Project(s): Our undergraduate students have conducted research using large nationally available datasets as well as internal patient databases. Students working with our team will utilize existing clinical databases either from our clinic or research trials to explore important clinical questions such as predicting healthcare utilization or improvement in symptoms.

Website: https://connects.catalyst.harvard.edu/Profiles/profile/1256363 and  https://www.bidmc.org/centers-and-departments/digestive-disease-center/services-and-programs/ibs-and-functional-bowel-disorders-program

Research: The Nonalcoholic Fatty Liver Disease (NAFLD) Research Center, directed by Dr. Rohit Loomba, invites undergraduate students to participate in our ongoing studies of NAFLD, the leading cause of chronic liver disease in the U.S. Our team conducts cutting-edge research on all aspects of NAFLD including non-invasive biomarkers, genetics, epidemiology, clinical trial design, imaging end-points, therapeutics, and integrated OMICs using microbiome, metabolomic and lipidomic analyses. For interested trainees, our center has an array of ongoing projects including: 

• A Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) study of the natural history of NAFLD (NIDDKU01DK061734).
• A screening study for advanced fibrosis in the diabetic population (NIDDK R01DK124318.
• A collaborative study with multiple research teams on the intersection between cardiovascular disease and NASH (NHLBI P01HL147835).
• A study of NAFLD in HIV patients (NIDDK R01DK121378).
• An international multicenter study to investigate whether changes in non-invasive imaging biomarkers predict disease progression and clinical outcomes in NAFLD.

Project(s): We offer students an unprecedented opportunity to learn firsthand about clinical research, epidemiological studies, biomarker development and clinical trial design in the context of NAFLD population. Students would have the opportunity to develop a thesis/capstone project and receive step-by-step guidance on study design, data analysis, and manuscript preparation. We are a highly diverse team who serves a multicultural patient population. Minorities and women are welcome and strongly encouraged to apply.

Website: http://fattyliver.ucsd.edu/

Research: The Margolis Lab studies the effects of neurotransmitters and inflammation on enteric nervous system development and function. The goal of Dr. Margolis’s research is to understand the enteric nervous system (ENS) and disorders that have in common an effect both on the brain and the gut, sometimes referred to as the “brain-gut axis.” She has published novel observations on the roles that enteric neurotransmitters (specifically serotonin and oxytocin) play in ENS development and how signaling from such neurotransmitters may, when abnormal, result in gastrointestinal (GI) disorders such as inflammatory bowel disease (e.g., Crohn’s disease and ulcerative colitis), motility dysfunction (e.g., chronic constipation or irritable bowel syndrome), and necrotizing enterocolitis (a devastating intestinal inflammatory disorder primarily of preterm infants). This research has recently provided important insights into how abnormalities of the ENS can arise in children with brain-gut axis disorders such as autism, antenatal antidepressant exposure, and irritable bowel syndrome.

Project(s): Students will work with mouse models of IBS, autism and antidepressant exposure.

Website: https://www.pediatrics.columbia.edu/research-labs/margolis-lab

Research: Epidemiology, clinical research of liver cancer, hepatitis B, hepatitis C, and fatty liver disease with a focus on understudied populations, socioeconomics, sex and ethnic disparities, disease prevention and treatment outcomes.

Project(s): This depends on students’ skill sets and interests. Examples of prior projects and publications by recent undergraduates include: (1) Zou B, Yeo YH, Nguyen VH, Cheung R, Ingelsson E, Nguyen MH. Prevalence, characteristics and mortality of obese, non-obese and lean non-alcoholic fatty liver disease in the U.S., 1999-2016. J Intern Med 2020. doi: 10.1111/joim.13069.  PMID: 32319718. (2) Vy H. Nguyen, Yee Hui Yeo, Biyao Zou, Michael H. Le, Linda Henry, Ramsey C. Cheung, Mindie H. Nguyen.. Discordance between actual weight, weight perception and weight loss intention among persons with NAFLD. Journal of Internal Medicine 2020. [In press]. (3) Ramrakhiani NS, Le M, Yeo YH, Le A, Maeda M, Nguyen MH. Validity of International Classification of Diseases, 10th Revision, Codes for Cirrhosis. Dig. Dis. 2020. doi: 10.1159/000510981. PMID: 32814313.

Website: http://med.stanford.edu/nguyenlab.html

Research: A remarkable feature of the GI tract is that it has its own intrinsic nervous system that can function rather independently to regulate a wide variety of digestive functions. The goal of our laboratory is to understand how neurons and glial cells in this enteric nervous system (ENS) interact with other cells in the gut to regulate motility and inflammation. We use mouse genetic models, in vivo and in vitro assays to tackle these questions. Our work is motivated by the conviction that a better understanding of enteric neurobiology will advance the diagnosis and treatment of digestive disease.

Project(s): The student will work on an independent project under the close mentorship of a postdoctoral fellow or senior Ph.D. student with the goals of learning how to design, perform and interpret experiments, give effective presentations, and contribute to a publication. Projects may involve cell culture, dissections, microscopy, and/or behavioral tests on mice depending on student’s interests and abilities.

Website: raolab.hms.harvard.edu

Research: Neurogastroenterology and motility– understanding the mechanisms of disease and novel diagnostics and treatments for irritable bowel syndrome (IBS), gas/bloating, constipation, fecal incontinence, and gastroparesis. Current projects in the lab include 1. TNT for fecal incontinence; 2. Gut and brain interactions; 3. Food intolerance; 4. SCBDS capsule for SIBO; 5. Magnetic treatments for gastroparesis.

Project(s): Students could work on projects (1) examining bidirectional gut-brain interactions in IBS and constipation, (2) dietary fructan intolerance, diagnosis and new enzyme therapy, or (3) body posture and defecation dynamic.

Research: We use stem cell biology and incorporate engineering techniques to better understand human liver disease, aiming to improve clinical therapy.

Project(s): On-site projects will involve stem cells and engineering. Remote projects will involve large datasets that the lab is working on.

Website: https://www.schwartzlabwcmc.com/

Research: Research in the lab aims to understand how intestinal epithelial cells sense and interact with their surroundings and how membrane channels and transporters contribute to immune function, host-microbial symbiosis, and cellular metabolism. Projects in the lab use a variety of approaches and span several aspects of physiology and disease, including both basic science and translational research. Our lab uses high resolution quantitative imaging, electrophysiology, organoids, and mouse genetic models to investigate the cellular environment. An important aspect of our research also involves the development of novel optical tools for studying tissue and cell biology.

Project(s): Cyclic di-nucleotides are messenger molecules produced by both host cells as well as the bacteria that occupy the gut. Recent data from our lab show that extracellular cyclic di-nucleotides can affect intestinal epithelial innate immune function through adenosine signaling. This project aims to to explore the role of extracellular cyclic di-nucleotides in shaping the epithelial response to viral signaling and virus entry.

Website: www.thiagarajahlab.com

Research: Inflammatory bowel disease (IBD), specifically crohn’s disease and ulcerative colitis. Recent studies defined factors associated with the development of Crohn’s disease after ileal pouch anal anastomosis, determined the value of histology in identifying Lynch syndrome in early-onset colorectal cancer patients, and compared the phenotype and genotype in adenomatous polyposis patients with and without a family history.

Project(s): Investigating the mechanisms of IBD in pregnancy.

Research: I am involved in clinical and translational research in Inflammatory Bowel Disease (IBD). Specifically, my main interests are in clinical outcomes and risk stratification among recently diagnosed IBD patients in order to understand the best way to care for patients early in their disease. In addition, I have an interest in the impact of COVID-19 on IBD patients, particularly the impact of IBD medications on COVID-19 outcomes. 

Project(s): Utilize existing databases or create new database through chart review to investigate risk factors for poor outcomes among recently diagnosed patients or IBD patients with COVID-19. Organize, analyze and write up research results for abstract and/or publication in peer-reviewed journal. Activities would likely involve study design, data extraction, data cleaning, database organization/creation, and basic data analysis. Potential for cross-sectional study as well in our IBD center (administering surveys to IBD patients for example). 

Website: https://www.mountsinai.org/profiles/ryan-ungaro