Changing Lives Through Research On the Job

Innovative Colorectal Research Targets Key Tumor-Suppressing Molecule

Candace Caldwell and Michael Varallo Last October, Candace Caldwell One of those friendly co-workers is made a big move—relocating from Michael Varallo, who started as the Portland, Oregon to Philadelphia to Department’s Business Manager on join the Department of Surgery. As the Christmas Eve 2018. It’s a role that Department’s first Operations Analyst, brought the 34-year-old South Philly she’s taking on a variety of evolving native full circle: he started working at responsibilities. Among them: data Jefferson at age 16 as a runner for the analysis and reporting, expense tracking Department of Surgery, a job he held

Researchers Scott Waldman, MD, PhD (left), and immunologist Adam Snook, PhD (right) have made tremendous and process improvement. through college. progress in colorectal research with the help of tissue samples provided by colorectal surgeon Scott Goldstein, MD (center) and his surgical colleagues in colorectal surgery. With a degree from Oregon State After graduating from Neumann University in Public Health, Health University with a degree in Finance, Management and Policy, Caldwell Varallo began working in Thomas If there were a “golden ticket” in the fight “We have mapped the mechanism enjoys using data to tell a story about Jefferson University’s Controller’s against colorectal cancer, it would be by which the hormones are lost,” guanylyl cyclase C (GCC) – a molecule Dr. Waldman explains. “It’s a reflection of current performance and identify Office. Since then, he has moved that plays a critical role in the suppression the very first mutation in the gene APC, opportunities to improve in the future. through progressively responsible of colorectal tumors. Most colorectal which triggers the cascade of events that She said she also enjoys collaborating positions within the Jefferson enterprise. tumors form or grow larger when GCC is leads to tumorigenesis. When APC is with her colleagues. As Business Manager, Varallo is silenced by the hormones that regulate it. mutated, a complicated signaling Researchers at Jefferson are working to mechanism shuts off the synthesis of For Caldwell, exploring a new city has responsible for planning and tracking find ways to manipulate these hormones these hormones.” The study’s hypothesis brought some surprises. For example, the Department’s budget and managing so GCC can get back to work suppressing is that dosing patients with commercially she’s still adjusting to Philly weather profit-and-loss statements to ensure tumors. available hormone analogs could help (Portland stays green in winter). Even revenues and costs are properly Leading the efforts are clinical turn GCC back on, halting development more surprising: the warmth and accounted for. or progression of colorectal tumors. pharmacologist Scott A. Waldman, MD, friendliness of her co-workers and Outside work, Varallo and his fiancée PhD, and immunologist Adam Snook, In addition to mapping how the neighbors. are settling in to a new home in the PhD, of the Waldman-Snook Laboratory. hormones are lost, Drs. Waldman and As they study GCC and the associated Snook want to understand the precise “People warned me about an abrupt, suburbs and planning their October hormones, Drs. Waldman and Snook signaling mechanisms that lead from cold attitude,” she recalls. “But that wedding. Looking to this next phase collaborate closely with colorectal activation of GCC to the prevention of hasn’t happened at all. Everyone is of his life, Varallo jokes, “I’ve put myself surgeons Scott D. Goldstein, MD, FACS, tumor initiation and progression. Another so nice.” on a budget!” Gerald A. Isenberg, MD, FACS, and study is supporting that effort, and again, Benjamin R. Phillips, MD, FACS, FASCRS, Drs. Goldstein, Isenberg and Phillips are as well as physicians from the Division contributing colon and rectal tissue of Gastroenterology. specimens to be studied in the lab. surgeons will be highly engaged in an “The Department of Surgery’s The team is studying these normal and “In the test tubes, we’re upcoming study involving patients with collaboration with the Waldman-Snook diseased samples both in animals and literally creating ‘mini active metastatic disease. Laboratory is helping to improve in test tubes. guts’ so we can get a good “With this study, we’ll take ‘killer’ immune outcomes and quality of life for those “In the mice, we’re letting the tumors read on what downstream cells from the patients’ own bodies and coming to Jefferson for care,” says Dr. grow to see if we can manipulate the molecular pathways genetically reprogram them outside the Goldstein. “Our team is at the forefront GCC and determine what signaling are being activated by the body to recognize the specific target – in of innovative colorectal cancer research.” mechanisms are being turned on or tumor-suppressing system.” this case, GCC being expressed on One such project is studying how off and what proteins are changing,” metastatic cancer cells,” Dr. Waldman commercially available gastrointestinal Dr. Waldman says. “In the test tubes, In addition to those studies, the explains. “We will create billions of those hormones could be deployed to combat we’re literally creating ‘mini guts’ so Waldman-Snook Laboratory is working genetically reprogrammed cells, and each colorectal cancer. Funded by the U.S. we can get a good read on what with colorectal surgeons on the second one will be a ‘smart bomb’ that ignites Department of Defense, the study is downstream molecular pathways phase of a colorectal cancer vaccine when it sees a target on a cancer cell in using tissue samples gathered by are being activated by the tumor- study that showed great promise in the lung or liver. In short, these ‘smart gastroenterologists during colonoscopies suppressing system. We couldn’t do Phase 1. Patient enrollment will begin in bombs’ will home in on the metastatic and by colorectal surgeons during any of this without our colleagues in late summer or early fall. Beyond that, cancer cells but won’t harm normal lung resections. Colorectal Surgery.” Dr. Waldman says the colorectal or liver cells.”

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