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.
December 23, 2020
In partnership with the Marks Lab, the Grossberg Lab was awarded the AACR Mark Foundation for Cancer Research “Science of the Patient” Award for their novel proposal, Autonomic dysfunction in cancer cachexia. Daniel L. Marks, M.D., Ph.D. (PI) and Aaron Grossberg, M.D., Ph.D. (Co-I) will evaluate the role of persistent activation and plasticity in the autonomic and neuroendocrine stress responses in pancreatic cancer cachexia in preclinical mouse models as well as in their multi-institutional observational clinical study. This is a 3-year grant providing a total of $750,000.
July 7, 2020
Aaron Grossberg, M.D., Ph.D., has been awarded a NCI Mentored Clinical Scientist Research Career Development Award (K08) for his Hepatic Metabolic Reprogramming Drives Pancreatic Cancer Cachexia proposal. Learn more about Dr. Grossberg's project here.
June 12, 2020
Aaron Grossberg, M.D, Ph.D.’s has been awarded a grant thru OHSU's Cancer Early Detection Advanced Research (CEDAR) for his unique proposal titled, “CoVID Prediction Hub of Oregon – U.S. County COVID-19 Prediction“. This project involves a computational approach to predict future CoVID hotspots based on characteristics we find to promote spread along with real-time crowdsourced fever measurements.
April 3, 2020
Brennan Olson, a current MD-PhD student affiliated with the Grossberg Lab recently received a RSNA Research Medical Student grant award (RMS2026) for his project titled Establishment & Validation of Cervical Vertebrae Muscle Wasting as a Marker of Sarcopenia for Patients with Head & Neck Cancer. Aaron Grossberg, M.D., Ph.D. serves on the doctoral thesis advisory committee for Mr. Olson. Congratulations to Brennan, Aaron, and their collaborators.
February 6, 2020
The Grossberg Lab was awarded a grant for their novel proposal titled “Heart Rate Variability for the Early Detection of Pancreatic Cancer”. Project Purple and the Cancer Early Detection Advanced Research Center (CEDAR) are co-sponsoring this novel work. While Dr. Grossberg is the PI, his collaborators include Diane Simeone, M.D. at NYU along with Tony Hollingsworth, Ph.D. and Kelsey Klute, M.D. at the University of Nebraska. Fitness trackers and is being sponsored by Project Purple. WHOOP fitness trackers will be utilized in this trial.
January 10, 2020
Aaron Grossberg, M.D., Ph.D. was interviewed by Project Purple on the Project Purple Podcast on his career journey and some of the exciting pancreatic cancer research. Project Purple works to raise awareness, support patients and families affected by the disease, and fund research efforts to defeat pancreatic cancer. Listen to the podcast here
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.
Diverging metabolic programmes and behaviours during states of starvation, protein malnutrition, and cachexia. Olson B, Marks DL, Grossberg AJ. J Cachexia Sarcopenia Muscle. 2020 Dec;11(6):1429-1446. doi: 10.1002/jcsm.12630. Epub 2020 Sep 28.
Toll-like receptor 4 mediates the development of fatigue in the murine Lewis Lung Carcinoma model independently of activation of macrophages and microglia. Vichaya EG, Ford BG, Quave CB, Rishi MR, Grossberg AJ, Dantzer R. Psychoneuroendocrinology, Volume 122, December 2020. https://doi.org/10.1016/j.psyneuen.2020.104874
Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma [published online ahead of print, 2020 Jul 19]. Grossberg AJ, Chu LC, Deig CR, Fishman EK, Hwang WL, Marks DL, Mehta A, Nabavizadeh N, Simeone DM, Weekes CD, Thomas CR. CA Cancer J Clin. 2020;10.3322/caac.21626. doi:10.3322/caac.21626
Quantitative 3D Photographic Assessment of Breast Cosmesis after Whole Breast Irradiation for Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Chapman BV, Lei X, Patil P, Tripathi S, Nicklaus KM, Grossberg AJ, Shaitelman SF, Thompson AM, Hunt KK, Buchholz TA, Merchant F, Markey MK, Smith BD, Reddy JP. Advances in Radiation Oncology 21 May 2020 https://doi.org/10.1016/j.adro.2020.04.035
Interleukin 6-independent metabolic reprogramming as a driver of cancer-related fatigue. Grossberg AJ, Vichaya EG, Gross PS, Ford BG, Scott KA, Estrada D, Vermeer DW, Vermeer P, Dantzer R.Brain Behav Immun. 2020 May 16:S0889-1591(20)30117-3. doi: 10.1016/j.bbi.2020.05.043. Online ahead of print.PMID: 32428555
Progression-free survival is a suboptimal predictor for overall survival among metastatic solid tumour clinical trials. Pasalic D, McGinnis GJ, Fuller CD, Grossberg AJ, Verma V, Mainwaring W, Miller AB, Lin TA, Jethanandani A, Espinoza AF, Diefenhardt M, Das P, Subbiah V, Subbiah IM, Jagsi R, Garden AS, Fokas E, Rödel C, Thomas CR Jr, Minsky BD, Ludmir EB.Eur J Cancer. 2020 Sep;136:176-185. doi: 10.1016/j.ejca.2020.06.015. Epub 2020 Jul 20.
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.
Quantifying the benefit of non-small-cell lung cancer immunotherapy. Ludmir EB, McCaw ZR, Grossberg AJ, Wei LJ, Fuller CD.Lancet. 2019 Nov 23;394(10212):1904. doi: 10.1016/S0140-6736(19)32503-6.PMID: 31777387 No abstract available.
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.PMID: 31220950 No abstract available.
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.
Author Correction: Imaging and clinical data archive for head and neck squamous cell carcinoma patients treated with radiotherapy. Grossberg AJ, Mohamed ASR, Elhalawani H, Bennett WC, Smith KE, Nolan TS, Williams B, Chamchod S, Heukelom J, Kantor ME, Browne T, Hutcheson KA, Gunn GB, Garden AS, Morrison WH, Frank SJ, Rosenthal DI, Freymann JB, Fuller CD.Sci Data. 2018 Nov 27;5(1):1. doi: 10.1038/s41597-018-0002-5.PMID: 30482902
Cancer exosomes induce tumor innervation. Madeo M, Colbert PL, Vermeer DW, Lucido CT, Cain JT, Vichaya EG, Grossberg AJ, Muirhead D, Rickel AP, Hong Z, Zhao J, Weimer JM, Spanos WC, Lee JH, Dantzer R, Vermeer PD.Nat Commun. 2018 Oct 16;9(1):4284. doi: 10.1038/s41467-018-06640-0.PMID: 30327461