Other Researcher Spotlight:
- Getting to know Craig Logsdon, PhD
- Getting to know Carrie Daniel-MacDougall, PhD, MPH
- Getting to know Joya Chandra, PhD
- Getting to Know Ann Klopp, MD, PhD
Craig Logsdon, Ph.D., and his research colleague, Zobeida Cruz-Monserrate, Ph.D., credit a large population of obese mice for providing insight into preventive, therapeutic and diagnostic options for minimizing the risk of pancreatic cancer. “By studying the relationship between a high-fat diet and cancer in mice with mutant KRAS, we are making headway into learning how both genes and the environment are key in the development of this lethal cancer,” explains Craig, a Professor in the Department of Cancer Biology at M.D. Anderson for the last 10 years.
“KRAS is a molecule that acts like a switch to turn on cellular activity. When KRAS is “on” it is like hitting the gas in your car- everything gets revved up. Everyone has KRAS genes, and as we age most people develop some KRAS genes that are mutated. The mutated version of KRAS is associated with cancer because the mutation affects how long it stays “on” after being activated. Mutated KRAS stays on much longer than the normal KRAS,” continues Craig. “Only mutated KRAS genes drive the development of cancer, but they don’t do it on their own. They must initially be stimulated to a fairly high degree. However, once KRAS activity is strong enough, then it is able to generate its own stimulants by causing inflammation. Inflammation of any kind is a great stimulant of KRAS activity, so obesity, smoking and other inflammatory-inducing activities are risky if mutant KRAS is present. The mutant KRAS in our bodies needs a ‘kick’ to turn bad, and anything that causes inflammation, can give that kick.”
“Pancreatic cancer is KRAS-dependent, and mutant, oncogenic KRAS isn’t always ‘on.’ But we now know that mice on a high-fat diet do get cancer, and that there is a direct correlation between obesity and cancer, which we have been studying in-depth.”
What is it about a high-fat diet that causes cancer? “A high-fat diet provides the stimulus needed to fully activate the oncogenic KRAS, which initiates inflammation in the pancreas at least in part by increasing the levels of COX2. We now have models of mice with mutated KRAS expression directed to their pancreas. Our studies show the mechanism by which a high fat diet induces cancer in these mice appears to involve activation of oncogenic KRAS, and the up-regulation of COX2, which promotes pancreatic inflammation. Importantly, COX 2 inhibitors prevent this process, which is an exciting finding regarding prevention. This may explain why daily aspirin has been found to be preventative in some studies, as it inhibits COX2.”
Born and raised in Oregon, Craig came to cancer research in mid-career, after studying pancreatic physiology at UC San Francisco and the University of Michigan, where he was a professor. “I worked with rodents for many years, and one day discovered that the process I was investigating was totally different in people. At that point, I decided to change directions and study people. My goal is to see if I might make a difference with the scientific knowledge I have while I’m still alive to see it happen,” he admits. Since assuming his endowed chair at MD Anderson, “we have learned a lot about mechanisms that increase risk for pancreatic cancer – even in children.” His current focus remains on pancreatic cancer and he is collaborating with Zobeida for studies on how to prevent this disease.
“It’s a slow process, but we are making progress and beginning to translate what we know to help patients in the clinical setting. We love to collaborate, and hope that by doing so, we’ll make a real difference and save more lives – sooner vs. later.”
As a nutritional epidemiologist and Director of M.D. Anderson’s Nutrition Research Group and CORE, Carrie Daniel-MacDougall, PhD, MPH, specializes in “population medicine,” researching variations among large free-living groups of individuals to study disease risk and discover new ways to improve outcomes in overall health. More specifically, she is focused on the role diet plays in cancer development and prevention, and the modifiable scientific mechanisms behind these relationships. “I have traditionally been interested in everything ‘up-stream’ of cancer, but I came to M.D. Anderson to shift some of my research toward also helping individuals who already have cancer.”
“Diet, energy balance and inflammation are common themes behind obesity and related chronic conditions – like – diabetes – that impact both cancer risk and survival,” she explains. She and her colleagues utilize ‘dietary assessment methodology,’ as well as novel biomarkers to identify new risk factors for both obesity and cancer. Some of the most informative findings have come from large, healthy U.S. populations followed long-term (10+years) for cancer outcomes, as well as from understudied international and minority populations with unique diet and lifestyle traits.
“Through studying diet, obesity and inflammation in the etiology of cancers of the kidney and digestive system, I have been drawn to a new field of research on the microbiome. I believe it offers an exciting tool as we look for new ways to target disease risk via diet,” she adds. “By sequencing the geonomes of bacteria living within the body, we are learning more about all the direct and systemic processes that these ‘bugs’ are involved in.” Using the framework of large epidemiologic studies of cancer risk, and linking into her colleagues’ expertise in molecular epidemiology, genomics and metabolomics, she hopes to integrate the microbiome, as another important ally in understanding and preventing cancer.
In one of her current collaborative studies, she is working with the endoscopy clinic to track the seemingly ‘normal’ patients who develop pre-cancerous colorectal polyps. “As part of a larger study, headed by my Chair, we are looking at screening patients’ habitual or long-term diet, lifestyle and medical histories and collaborating with a lab at Baylor to sequence their gut microbiomes.” This is just the first step, as Carrie and her colleagues want to continue to design new studies, share experiences and find new mutually-beneficial collaborations. “I love working with our inspiring clinicians, and look forward to continuing to learn about their approach to patients and how to better tailor research to support their efforts.”
A native of Tucson, Carrie was interested in the impact diet plays in health from a young age, thanks to her mother, who became a real ‘health nut’ when Carrie was growing up in the 1980s. “Around my age (30s), my mother lost her sister to late stage breast cancer and her mother – my grandmother – to cardiovascular disease.” Carrie earned her BS in Molecular and Cellular Biology from the University of Arizona, and was planning to become a premed student, when she was exposed to epidemiology. “I loved the field, and decided that was the direction my life should take,” she recalls. She subsequently earned her MPH and Ph.D in Nutritional Epidemiology from Emory University, “a wonderful, interdisciplinary program.” She did part of her pre-doctoral research at the American Cancer Society and went on to a post-doctoral research fellowship at the NCI. In the summer of 2012, she moved from Washington, D.C., to Houston, with her husband and pet Dalmatian to join M.D. Anderson, where they soon welcomed their first child. She is excited about building a core of colleagues to study diet and cancer in new ways. “Fortunately, the concept of diet and nutrition is totally accessible – our goal is to find the most meaningful and safe ways to apply what we know on a public health level.”
A cell biologist and long-time leukemia researcher, Joya Chandra Ph.D.’s mantra is simple, yet profound: “Our diet is a modifiable and incredibly powerful tool for augmenting cancer treatments and controlling and reducing risk in cancer survivorship. And a nutritionally-sound diet is accessible to us all.”
Since joining M.D. Anderson’s Children’s Cancer Hospital in 2002, Dr. Chandra and her team of researchers have studied the impact of oxidative stress (OS) in both treating and preventing cancer. “We try to increase OS to enable chemotherapy to selectively kill cancer cells, which already have a higher level of OS,” she explains. “Conversely, we want to block or decrease OS in cancer cells to keep them from growing, on the prevention side.”
Changing OS “at the organismal level,” is feasible through diet and nutrition. By studying nutrition and measuring OS in pediatric leukemia patients, Dr. Chandra wants to understand how micronutrients and certain OS-increasing diets may enable chemotherapies to work more effectively. To help parents and families determine what foods are most beneficial for their children, Dr. Chandra and her team launched the “ON to Life Program,” an instructional program developed for The Children’s Cancer Hospital that teaches healthy lifestyle techniques, provides resources for tolerating treatments and offers a virtual cookbook of customizable, easy to make recipes that promote optimal nutrition, weight loss and healthy eating habits for pediatric cancer patients, survivors and their families.
“We know that patients on steroids often gain weight, and obesity places them at higher risk for other cancers and cardiovascular problems down the road,” explains Dr. Chandra. “By guiding families through the ON to Life Program and supporting them with dieticians and actual real-world tested healthy recipes, we can instill healthy eating habits as a lifestyle, early-on.” The on-line cookbook, “At the Table,” can sort foods that may help minimize certain symptoms, while also fulfilling FDA requirements for diets, and sound nutrition.
Additionally, her team is collaborating with experts who have designed video games for kids to learn about “energy balance,” the need to eat healthfully, exercise regularly and gain strength in a comprehensive, coordinated way. A new game specifically designed for pediatric cancer survivors is in the works. “We are using our cookbook, video games and personalized diet and exercise plans to help children seen at the pediatric clinic, and we routinely include parents in these initiatives,” shares Dr. Chandra. “The electronic cookbook has been welcomed as a useful resource by families of our patients. It’s all openly available on our website, and can be viewed on tablets, iPads and smartphones,” she adds. “Ultimately, we would like to deliver our message, change diets and measure the impact it has in/on cancer patients.”
Dr. Chandra is well-suited to the multi-disciplinary role she plays as a researcher and educator. She grew up in New Orleans and is a graduate of Louisiana State University and the University of Texas School of Biomedical Sciences, where she received her Ph.D. in cancer biology and immunology. She studied toxicology at the Karolinska Institute in Stockholm, Sweden, and did her second post doc at the Mayo Clinic. “I was first introduced to research on late effects of cancer therapy in pediatric patients in the M.D. Anderson summer program for college students. After graduating from LSU with a degree in microbiology, I worked as a lab tech at Baylor, prior to joining the University of Texas Health Science Center at Houston Graduate School of Biomedical Sciences. I realized how much I enjoyed research, and I’ve never looked back.”
Today, Dr. Chandra is a highly-published principal investigator, teacher and mentor to pre and postdoctoral fellows. She has won numerous awards for her work on apoptosis and OS. She is open to collaborating on using OS as a biomarker for diet-related behavioral change, and ideally, including her cookbook as part of a clinical trial.
“I am interested in the power of food to make a positive impact in the lives of our patients. We want to take the knowledge out of the lab and apply it directly to those we counsel and treat as soon as we can.”
Ann Klopp has always been a “research person,” who also enjoys face-to-face patient care. Today, she conducts translational research, lab studies which are designed with a goal of improving clinical treatments.
A radiation oncologist, Dr. Klopp and her team study how obesity influences stem cells in abdominal/visceral fat, tracking how these cells migrate into tumors, form supporting stroma and drive cancerous tumor growth in heavier patients. She has focused both her research and clinical work on women’s health, in particular, endometrial, ovarian and cervical cancer. “Today, we’re much closer to learning how obesity impacts the development and recurrence of gynecologic cancer,” she explains.
Dr. Klopp isolates visceral adipose stem cells from the omentum, and compares these cells to stem cells from other tissue sources to see how these cells can promote endometrial and ovarian cancer. “We’ve discovered that visceral adipose-derived stem cells (ASC) promote the growth of endometrial cancer,” she explains. “We are able to see differences in stem cells from mice which are fed a high-fat diet, vs. a low-fat diet, and we are investigating how ASC drive tumor growth in obesity. We are isolating stem cells from both obese and thin patients to learn more about how obesity alters stem cells in patients.”
Dr. Klopp and her team use unique software for measuring the volume of visceral adipose in ovarian cancer patients. The technology is able to distinguish fat tissues from fluid, soft tissue, gas and bone in order to develop a highly accurate measure of visceral adipose. “In the short-term, we hope to determine whether obesity impacts outcome in endometrial and ovarian cancer, and in the long-term, we hope to understand exactly how this happens,” she explains. Research-wise, Dr. Klopp is interested in collaborating with others who are studying the prognostic effects of visceral adiposity and mechanisms by which obesity promotes cancer progression. Clinically, Dr. Klopp is also interested in the management of advanced endometrial cancers and the use of advanced radiation techniques to minimize toxicity.
Dr. Klopp, a graduate of the University of Michigan and the Medical College of Wisconsin, earned her MD and PhD in Microbiology and Molecular Biology. In addition to her research and clinical work, she serves as a moderator for The Center for Energy Balance Journal Club and enjoys mentoring trainees in both clinical and translational research. A native of Milwaukee, she is married with three young children, and enjoys swimming, traveling and reading in her spare time. Dr. Klopp arrived in Houston eight years ago to do her residency, and “never left.” “I feel fortunate that the work I do in research and clinical oncology is both intriguing and gratifying,” she claims. Which is lucky for us all, indeed.
Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors.
Klopp AH, Zhang Y, Solley T, Amaya-Manzanares F, Marini F, Andreeff M, Debeb B, Woodward W, Schmandt R, Broaddus R, Lu K, Kolonin MG.
Clin Cancer Res. 2012 Feb 1;18(3):771-82.
Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth?
Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd.
Stem Cells. 2011 Jan;29(1):11-9. doi: 10.1002/stem.559. Review.
Mesenchymal stem cells promote mammosphere formation and decrease E-cadherin in normal and malignant breast cells.
Klopp AH, Lacerda L, Gupta A, Debeb BG, Solley T, Li L, Spaeth E, Xu W, Zhang X, Lewis MT, Reuben JM, Krishnamurthy S, Ferrari M, Gaspar R, Buchholz TA, Cristofanilli M, Marini F, Andreeff M, Woodward WA.