UConn Health Is on the Frontier of Colon Cancer Research

The Colon Cancer Prevention Program (CCPP) was created in 2006 by Dr. Joel Levine and Dr. Daniel Rosenberg. It was among the first clinical–translational programs directed to the study of the risks for colon cancer, the earliest changes in colon cell biology, and the implications for risk reduction and long-term prevention. With Dr. Rosenberg as Scientific Director and Dr. Levine as Clinical Director, the CCPP was the first to develop an endoscopic methodology to detect the earliest colon surface changes, Aberrant Crypt Foci (ACF). Dr. Tom Devers in the Division of Gastroenterology began translational collaborations with the Rosenberg Laboratory starting in 2010, and Dr. John Birk and Dr. Haleh Vaziri have continued these collaborations. In particular, we all deeply miss the humanity and scholarship of the late Dr. Devers.

The Rosenberg Laboratory in the Center for Molecular Oncology is a leader in novel investigations related to improving early detection of cancer, developing population-based studies of colon cancer risk, including inflammatory bowel diseases, and developing effective chemoprevention strategies for the treatment of high-risk individuals. Dr. Rosenberg’s research extends across a wide range of research topics in colon cancer biology, applying a variety of mouse genetic cancer models to further our understanding of carcinogenic mechanisms, eicosanoid biology, and the application of new chemoprevention approaches. His ongoing studies sponsored by the NCI and American Institute of Cancer Research, in collaboration with GI and Dr. George Weinstock at The Jackson Laboratory, have so far shown the salutary influences of dietary walnuts with effects on urolithin production, inflammation and colon microbiome diversity. Dr. Masako Nakanishi’s research in the Rosenberg Lab focuses on examining the role of bioactive lipid signaling in colon carcinogenesis as well as therapeutic interventions and nutritional modulation of cancer risk.

The CCPP model has been to engage patients, over time, with a focus on individual risk profile, detailed interpretation of their colonoscopy findings and a related long-term prevention plan. CCPP has studied the consequences of low Vitamin D levels on the higher risks for colon polyps. Vitamin D supplementation is now a common recommendation for risk reduction of various malignancies and inflammatory diseases. The CCPP also advises patients on dietary changes, over time, that seek to prevent the shifts in colon bacteria populations that favor colon polyps and cancer. To enhance early detection of colonoscopic interval polyps, the CCPP introduced the first US quantitative fecal immuno-hemoglobin test (FIT). This is consistent with our longitudinal risk modulation clinical–laboratory approach. Currently, in collaboration with Dr. Joseph Anderson and colleagues at Dartmouth Medical Center and East Carolina Medical University, we are examining a vast data set of FIT in 3000 at-risk patients over a decade. Consistent with our goal of translational clinical and basic science, the Srivastava Lab is studying gene expression and the biologic context of when a polyp becomes FIT +.

Other complementary approaches to the study of colon cancer are taking place at UConn Health and UConn Storrs. Dr. Christopher Heinen’s laboratory in the Center for Molecular Oncology studies a condition called Lynch syndrome, which is the most common hereditary form of colorectal cancer. This disease is caused by inherited mutations in genes of the DNA mismatch repair (MMR) pathway. The MMR pathway normally corrects mistakes made by the cell when attempting to copy its DNA during division. The Heinen lab is running multiple NIH-funded studies to understand how defects in the MMR pathway could cause a cell to become cancerous. They use various cutting-edge approaches including CRISPR gene editing to re-create patient mutations as well as human colonic organoids, which are like tiny little human colons in a plastic dish, to study how loss of the MMR pathway affects colon biology.

Dr. Charles Giardina’s lab in the Department of Molecular and Cell Biology is looking at colon cancer in young patients, which is disturbingly on the rise. These cancers are often discovered at an advanced stage, suggesting that they progress rapidly. We are pursuing studies to understand the role of fibroblasts obtained on colonoscopy here at UConn Health in early onset colorectal cancer to determine their contribution to cancer progression in young patients. Knowledge from these studies may help identify high-risk individuals and suggest approaches to prevent early onset colorectal cancers. In another more basic cancer cell biology project, we are studying how colon cancer cells successfully navigate mitotic checkpoints. Unlike normal cells, cancer cells have aberrant chromosomes and actively suppress mitotic checkpoints to divide. Understanding how cancer cells overcome mitotic checkpoints could suggest new approaches for colon cancer treatment.

None of this would have been possible without our patients and the remarkable staff that has been so devoted to explanation, education, science and the human connection here in the Division of Gastroenterology, the CCPP, and the Center for Molecular Oncology/Neag Comprehensive Cancer Center.

The Division of Nephrology has grown from a faculty of 5 to now 9 with more growth expected in the next year under the leadership of Dr. Yanlin Wang, M.D., Ph.D., FASN, an internationally recognized leader in Nephrology. The mission of Nephrology is to provide state-of-the-art care to our patients and innovative education for the next generation of healthcare professionals and conduct cutting-edge research related to nephrology.

Patient Care

We are committed to provide state-of-the-art, patient-centered, personalized care for kidney disease including diabetic kidney disease that can progress to kidney failure and the need for dialysis and kidney transplant, hard-to-treat hypertension, genetic kidney diseases, kidney stones, primary glomerular disease, immune diseases such as systemic lupus erythematosus or an allergic drug reaction that affects the kidney. Given the diverse range of presentations with kidney disease, the UConn nephrologists see patients in many settings: the hospital including intensive care unit, the office (both main campus and the Canton), and ambulatory dialysis centers in Farmington, Avon, and Manchester. Avon Dialysis Center was opened in October of 2019, which has been selected to provide dialysis for COVID-positive patients since the pandemic. We have opened an outpatient Therapeutic Plasma Exchange Clinic since July, 2020.  This clinic is located in Post-Anesthesia Care Unit (PACU) on the first floor of the University Tower, which allows patients in need to have same-day outpatient plasmapheresis treatment thus avoiding a lengthy inpatient hospital stay. See detailed information about our outpatient Therapeutic Plasma Exchange Clinic.

Research

The Division of Nephrology is actively involved in a wide range of research areas including basic science program in acute kidney injury and chronic kidney disease, outcomes of dialysis and therapeutic apheresis, scholarly reports of unusual or rare disorders, systematic evaluation of chronic periodontal disease in our population of chronic kidney disease. Each faculty member seeks to collaborate with colleagues to enhance new knowledge of kidney disease and education. Our research activities are funded by grants from the National Institutes of Health, the Department of Veterans Affairs, private foundations, and pharmaceutic companies.

Education

Nephrology faculty actively participate in education and training for first-year medical students through graduation, for internal medicine residents and for nephrology subspecialty training. Continuing Medical Education (CME) is also a large part of what we do, with local conferences including Medicine Grand Rounds, departmental CME courses and the Greater Hartford Nephrology Conference. Clinical electives for medical students and residents are organized to include both inpatient consultative nephrology as well as ambulatory nephrology exposure. We host visiting medical students and residents, as well as provide rotations for graduate nursing students in the APRN programs at UConn Storrs.

The New England Sickle Cell Institute

The Hematology/Oncology Service has grown from a faculty of four to now eight with more growth expected in the next year. Our Hematology service has gone from 2 to 5 faculty with growing expertise in coagulation (thrombosis and hemostasis), hemoglobinopathies in particular sickle cell anemia, hematologic malignancies, immune cytopenias and bone marrow failure disorders. Close collaboration and partnership with hematopathology in both coagulation and malignant hematology enhance patient care and growing regional expertise. We support many growing programs at the health center including the building of a thoracic oncology, melanoma and neuro-oncology programs. Additionally, we participate in clinical/translational trials with colleagues across both UConn Health and the Storrs campus. Ten nurse practitioners support our program and make it stronger allowing faculty to play significant roles in education and research.

The New England Sickle Cell Institute is our most successful program with proven excellence in research, education and clinical care not only at UConn but also nationally and internationally. It has served as a model throughout the world for the care of this underserved population. Its existence is due to the vision and hard work of Dr. Biree Andemariam. Some accomplishments are:

Clinical

• 325 patients (largest in New England); acute and chronic disease management as well as care coordination, mental health services, and multi-disciplinary care for comorbidities
• Referrals statewide, regional, and national
• March 2020 established state’s first crizanlizumab infusion program (FDA-approved 11/2019 for VOC frequency reduction)
• Despite pandemic and temporary physical move x 2, clinic operations maintained including apheresis, transfusion, infusion, and acute pain management
• Rapid and sustained implementation of telemedicine to maximize safety of this vulnerable patient population

Research

• 4 therapeutic clinical trials accruing in 2020
  • Leading enrollment site in U.S. for phase2A IMR-687 trial (n=10 subjects); Andemariam global PI
  • Trial endpoints include safety/tolerability, fetal hgb induction, VOC reduction, priapism reduction
  • 3 new trials to open in 2021 including acute inpatient VOC anti-P-selectin monoclonal antibody therapy
• 3 federally-funded grants (HRSAx2; PCORI)
• $667,000 research funding in FY 2020 alone

Publications

• 6 peer-reviewed manuscripts in 2020 (includes Blood Adv., Lancet Haematol., British J. Haematol., Ann Hemtol.)

Oral Presentations

• 8 peer-reviewed oral abstracts national/international meetings; 8 peer-reviewed posters
• 19 invited national/international presentations

Grants

• State of Connecticut Department of Public Health (PI: Andemariam; UConn Health) Connecticut Sickle Cell Disease Initiative
• American Society of Hematology (PI: Andemariam; UConn Health) American Society of Hematology Research Collaborative Sickle Cell Disease Clinical Trials Network
• HRSA 17-078 (PIs: Stewart/Lanzkron; Johns Hopkins University) Sickle Cell Disease Treatment Regional Collaboratives Program
• PCORI (PIs: Rubin/Smith-Whitley; Children’s Hospital of Philadelphia) Management of Care Transitions for Emerging Adults with Sickle Cell Disease Care: The COMETS Study

Awards

• Genice T. Nelson, DNP, APRN—Florence Nightingale Award
• Biree Andemariam—Sickle Cell Disease Association of America, Inc. Chairman’s Award

Highlights

• Andemariam invited to present at United States Congressional Hearing on “Current State of Sickle Cell Disease” (October ‘20)
• Andemariam appointed to United States Department of Health and Human Services Advisory Committee on Blood & Tissue Safety & Availability (August ‘20)
• Andemariam appointed to prestigious American Society of Hematology Scientific Committee on Red Cell Biology (December ‘20)
• Nelson and Dr. Andemariam served on national planning committee of 2020 Sickle Cell Disease Assoc. of America Annual Convention and Scientific Symposium (October ‘20)

Dr. Andemariam led an international committee of 33 medical/scientific experts in developing Guidelines for the Management of COVID in Individuals with Sickle Cell Disease. Dr. Nelson served on this committee.

UConn Health International Travelers’ Medical Service

Travel is back!

During the darkest moments of the pandemic, each of us has longed to be away from our Zoom world, out of lockdown, and enjoying freedom of movement with the possibility to go on new adventures or visit loved ones abroad. Although the pandemic is still quite active in many parts the developing world, the United States may be emerging from the worst of the pandemic and international travel is slowly rebounding. The UConn Division of Infectious Diseases is poised to meet our travelers’ needs as the world re-opens to a radically altered travel environment.

The restructuring of work culture during the pandemic has given way to unintended consequences including the reframing of the concept of leisure, with the realities of post-pandemic travel likely to not only include the realities of wide-ranging COVID regulations, but also a focus on “low travel” (ground transportation such as trains and buses), less frequent but longer stays, and a general change in ethos from quantity of locations experienced to a greater quality of an experience that may have greater immersion at fewer locations.

Drs. Nina Carley, Kevin Dieckhaus, and Mary Snayd operate the UConn International Travelers’ Medical Service, with sites in West Hartford and Farmington. This service has been an operation since 1984 and has evaluated over 1100 patients annually prior to the near-complete shutdown of international travel due to the pandemic. With the recovery of the travel industry and increased international bookings, the International Travelers Medical Service has responded by increasing the availability of travel related consultations. The travel consultation entails a detailed analysis of travel-related health risks based on itinerary, planned activities and exposures, and personal health conditions. Based on these factors, we develop a detailed and personalized preventive health plan.

The clinic stocks a wide variety of vaccines that may be required for maintain good health in low-resourced areas. The clinic is an official Yellow Fever Vaccination Center. Yellow fever vaccine, which is mandatory for entry into some countries in South America and Africa, had been unavailable due to manufacturing shortage since 2018 but is now back in stock and available. Other vaccines for Hepatitis A, Japanese encephalitis, typhoid, polio, rabies, meningitis, hepatitis B, and tetanus are available on site for immediate administration as indicated. For travelers going to areas with malaria, prescriptions for appropriate malaria medications will be provided with other prevention strategies. Medications for management of travelers’ diarrhea, the most common medical event associated with travel, are also provided. Country-specific guidance on COVID-19 regulations are discussed in detail to allow appropriate planning of itineraries, medical testing and contingency plans.

Travelers should ideally plan to be evaluated 6 to 8 weeks before anticipated departure to allow adequate time for vaccination to be effective. Patients may be seen in-person with on-site inoculations, or by telemedicine with follow-up nursing appointments scheduled for any inoculations that may be necessary. Families traveling together are encouraged to be evaluated as a group. Adults and children 16 years of age or older may be seen in Farmington. Children and families with children can be seen in West Hartford. To make an appointment with the International Travelers’ Medical Service, please call 860-679-2411 or refer through Epic as “Ambulatory Referral to Travel Clinic”.