Aaron Grossberg, M.D., Ph.D. is an assistant professor of radiation medicine. Dr. Grossberg’s practice focuses on cancers of the pancreas and breast. He is interested in the use of stereotactic body radiation therapy (SBRT) for treatment of both early and locally-advanced pancreas cancer with an emphasis on genetic and molecular factors that affect toxicities after radiation therapy. In a joint appointment with the Cancer Early Detection Advanced Research Center and the Brenden-Colson Center for Pancreatic Care, Dr. Grossberg studies the interaction between cancer and metabolism in an effort to identify ways to diagnose cancers sooner and improve the quality of life of cancer patients.
His laboratory is working to understand how cancer impacts the global metabolic balance of the organism. They are defining how a localized tumor disrupts normal nutrient partitioning and the effects of this interaction on physiology, behavior, and adaptation.
By considering cancer in the context of its macroenvironment, Dr. Grossberg hopes to translate our insights into new approaches to early detection, risk stratification, and treatment of lethal malignancies.
Cancer is made up of aberrantly proliferating cells, which fail to respond appropriately to the normal regulatory mechanisms that impede growth. To grow tumors must acquire an adequate supply of building blocks to manufacture the macromolecules needed for cell growth and division. Research focused on how cancer cells repurpose cellular metabolism to promote proliferation has revealed incredible plasticity, allowing cancer cells to remain anabolic in a broad range of nutrient contexts. Universally, tumors must usurp the nutritional resources from the body and repurpose them for tumor cell growth. In its most advanced stages, this is evidenced by the wasting syndrome, cachexia, which is characterized by muscle and organ wasting, weight loss, and depleted physiologic reserve. Nutritional supplementation is ineffective in reversing cachexia, implying that cancer enacts a devastating metabolic program. Defining this process in early stages of tumor development, when cachexia could be prevented or reversed, has remained an elusive task. Despite recognition as a fundamental component of tumor growth, how cancer redirects metabolic resources from the host, and the impacts of this process on tumor growth, symptoms, and patient resilience remain poorly understood. We aim to define the biobehavioral signature of early cancer development and metabolic reprogramming and to identify the key pathways underlying this phenomenon.
Our laboratory focuses primarily on pancreatic cancer, among the deadliest and most metabolically disruptive tumors. Pancreatic ductal adenocarcinoma (PDAC) is currently the 4th leading cause of cancer death, with fewer than 10% of PDAC patients alive 5 years after diagnosis. Physicians are seldom alerted to a problem in the pancreas until advanced tumors have developed, so most patients present at an unresectable, and thus incurable, stage of disease. Although the majority of cases are sporadic, there are currently no effective screening strategies for the population. PDAC is often preceded by adult onset diabetes and is commonly associated with cachexia at diagnosis, implicating early metabolic reprogramming as a defining feature. Decreased total daily activity is among the first observed signs of sickness in humans and preclinical animal models of acute and chronic diseases. Asthenia, the symptomatic surrogate for decreased activity, is the most common presenting symptom of PDAC, reported by nearly 90% of patients with localized disease. We believe that this reflects a sensitive behavioral measure of metabolic reprogramming. We utilize orthotopic and genetic mouse models of PDAC to identify early behavioral and physiologic signatures of cancer development. We are also evaluating mHealth approaches to identifying patterns associated with cancer development in high risk PDAC populations. Working with our colleagues in the Cancer Early Detection Advanced Research Center and Brenden Colson Center for Pancreatic Care to we aim to define the molecular and biochemical fingerprint of early PDAC in both mouse models and clinical samples.
Our current interest is in identifying novel physiometric approaches to PDAC screening. We are also interested in how cancer growth effects whole body metabolism and the role this plays in physiologic reserve and adaptation to metabolic challenges. Through this work, we hope to advance understanding of tumor-host crosstalk and its relationship to tumor growth, patient resiliency, and quality of life.
Heike Mendez, B.S., Research Associate
Heike Mendez is a senior research assistant at Oregon Health and Science University working in the Grossberg Lab. Ms. Mendez holds a bachelor's degree in molecular biology from Liese-Meitner Scientific Institute.
September 30, 2019
Aaron Grossberg, M.D., Ph.D. has been invited to speak at the Seventh JCA-AACR Special Joint Conference on the Latest Advances in Pancreatic Cancer Research: From Basic Science to Therapeutics. This prestigious conference will take place from June 9-11, 2020, at the Kyoto Tokyu Hotel in Kyoto, Japan. Dr. Grossberg will present in the session entitled “Metabolism, anti-oxidants, and cachexia. Congratulations to the Grossberg Lab!
September 10, 2019
Aaron Grossberg, M.D., Ph.D. and was named one of eight 2019 Lamfrom Laureates. These award supports promising early-stage cancer researchers at OHSU.
August 26, 2019
Mara Rosenberg has been awarded a research grant from the Radiological Society of North America to study cachexia, a severe form of muscle wasting, in patients with pancreatic cancer. Ms. Rosenberg is using computed tomography scans to track muscle loss and she is correlating these imaging results with next generation sequencing to identify mutations and other gene alterations that influence the development of cachexia. Her goal is to reveal details about the mechanisms driving cachexia, which could open new paths for treatment. Her mentor is Aaron Grossberg, M.D., Ph.D., an assistant professor in the Department of Radiation Medicine.
The Trials (and Tribulations) of Complementary and Alternative Medicine in Oncology. Ludmir EB, Jethanandani A, Mainwaring W, Miller AB, Lin TA, Espinoza AF, Verma V, VanderWalde NA, Grossberg AJ, Guadagnolo BA, Koong AC, Jagsi R, Thomas CR, Fuller CD. J Natl Cancer Inst. 2019 Jun 4. pii: djz117. doi: 10.1093/jnci/djz117.
Lipocalin-2 is dispensable in inflammation-induced sickness and depression-like behavior. Vichaya EG, Gross PS, Estrada DJ, Cole SW, Grossberg AJ, Evans SE, Tuvim MJ, Dickey BF, Dantzer R. Psychopharmacology (Berl). 2019 Feb 26. doi: 10.1007/s00213-019-05190-7.
Enteral Activation of WR-2721 Mediates Radioprotection and Improved Survival from Lethal Fractionated Radiation. Molkentine JM, Fujimoto TN, Horvath TD, Grossberg AJ, Garcia CJG, Deorukhkar A, de la Cruz Bonilla M, Lin D, Samuel ELG, Chan WK, Lorenzi PL, Piwnica-Worms H, Dantzer R, Tour JM, Mason KA, Taniguchi CM. Sci Rep. 2019 Feb 13;9(1):1949. doi: 10.1038/s41598-018-37147-9.
Assessing the Impact of Complementary and Alternative Medicine Trials in Oncology. Ludmir EB, Jethanandani A, Mainwaring W, Miller AB, Lin TA, Espinoza AF, Grossberg AJ, Fuller CD. Integr Cancer Ther. 2019 Jan-Dec;18:1534735419859089. doi: 10.1177/1534735419859089. No abstract available.
Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase. Vichaya EG, Laumet G, Christian DL, Grossberg AJ, Estrada DJ, Heijnen CJ, Kavelaars A, Dantzer R. Neuropsychopharmacology. 2019 Jan;44(2):364-371. doi: 10.1038/s41386-018-0075-z. Epub 2018 Apr 27.