Research Interests and Ongoing Research
Cachexia is a metabolic condition characterized by progressive skeletal muscle and body weight loss and affects up to 80% of cancer patients. This loss of skeletal muscle mass contributes to muscle weakness, increased fatigue, decreased quality of life, reduced tolerance to cancer therapies and increased mortality. In this regard, our lab is focused on better understanding the mechanisms which lead to the initiation and progression of muscle wasting in response to tumor burden. One signaling pathway we have remained focused on in skeletal muscle is the Forkhead boxO (FoxO) signaling pathway as it broadly relates to muscle wasting. Indeed, an increase in FoxO is sufficient to cause skeletal muscle fiber atrophy and FoxO-dependent transcription is necessary for muscle atrophy induced by tumor burden, and in response to multiple other pathophysiological conditions. Therefore understanding the upstream activators and downstream targets of FoxO in skeletal muscle is critically important and a primary focus of our studies. These studies focus not only on identifying causative factors in the atrophy process, but also on broader aspects of tumor-induced skeletal muscle pathology including regenerative deficits and impaired structural integrity. Moreover, our work in this area also includes the study of other transcriptional networks which we have identified crosstalk with the FoxO signaling pathway to regulate muscle pathology. In a second line of work that also directly relates to cancer cachexia our lab is identifying soluble mediators released from tumor cells and/or the host in response to the tumor, and further studying how these mediators regulate the cachectic phenotype in skeletal muscle.
Lab Personnel
Andrew Judge, PhD
- Office: Biomedical Sciences Building J396
- Phone : 352-273-9220
- e-mail: arjudge@phhp.ufl.edu
- Mailing address: 101 S. Newell Drive, PO Box 100154, University of Florida, Gainesville, FL 32610
- Lab: Biomedical Sciences Building J303
Sarah Judge, PhD
- Office: Biomedical Sciences Building J399
- Phone : 352-273-9146
- e-mail: smsenf@phhp.ufl.edu
- Mailing address: 101 S. Newell Drive, PO Box 100154, University of Florida, Gainesville, FL 32610
- Lab: Biomedical Sciences Building J301
Graduate Students
Rachel Nosacka, BA
Rachel is a PhD student in the Interdisciplinary Program in Biomedical Sciences, Cancer Biology concentration. She entered the program in 2014. Rachel is a 2015-2017 recipient of the Clinical and Translational Science Institute TL1 Predoctoral Training Program Fellowship. She is studying skeletal muscle pathology in pancreatic cancer patients and in various preclinical models, with a focus on transcription factors which mediate gene repression and the physiological consequences of this repression in tumor bearing hosts
Former Lab Members
Brandon Roberts
PhD student, 2012-2016. Brandon is currently a post-doc at the University of Alabama, Birmingham
Adam Beharry, PhD
PhD student, 2011-2015. Adam is currently an Athlete Biological Passport Manager at the United States Anti-Doping Agency
Dan Ryder, PhD
Post-doc, 2012-2015. Dan is currently a Business Development Manager and Life Sciences Consultant at Thomson Reuters
Sarah Senf, PhD
PhD student, 2007-2012. Sarah is currently a Research Associate and Adjunct Faculty in the Department of Physical Therapy, University of Florida
Sarah Reed, PhD
Post-doc, 2009-2011. Sarah is currently an Assistant Professor of Animal Science at the University of Connecticut
Pooja Sandesara
Technician, 2009-2012. Pooja is currently in Dental School at Lake Erie College of Osteopathic Medicine in Bradenton, FL
Undergraduate Students
Meghan Murphy
Honors student, 2016-2017
Awards: 2016-2017 University Scholars Program Award
Jonathan Heaven
Honors student, 2016-2017
Awards: 2016-2017 University Scholars Program Award
Uttsav Sandesara
Honors student, 2014-2015
Awards: 2015 Undergraduate Dean’s Scholar Award
Travis Howard
Honors student, 2011-2012
Awards: 2011-2012 University Scholars Program Award
2012 Outstanding Undergraduate Research Award
2012 Undergraduate Dean’s Scholar Award
Jaina Moira
Honors student, 2010-2011
Awards: 2011 Undergraduate Dean’s Scholar Award
2011 Outstanding Undergraduate Research Award
Active Grants as PI/co-PI
2017-2020, Florida Department of Health Bankhaed Coley Research
Initiating mechanisms of cancer cachexia
PI
2016-2018, University of Florida Opportunity Seed Fund
Progressive carcinomas secrete GDF11 to induce cachexia
Co-PI
2016, University of Florida Health Cancer Center/Institute on Aging Cancer-Aging Collaborative Team Grant
Common mechanisms and biomarkers in sarcopenia and cancer cachexia
Co-PI
2015-2018, R21CA194118, NIH, NCI
Dysregulation of sarcomere stabilizing proteins cause muscle atrophy and weakness during cancer cachexia
PI
2011-2017, R01AR060209, NIH, NIAMS
FoxO signaling and skeletal muscle atrophy
PI
Select Publications (for full list click here)
Delitto D, Judge SM, Delitto AE, Nosacka RL, Rocha FG, DiVita BB, Gerber MH, George TJ Jr, Behrns KE, Hughes SJ, Wallet SM, Judge AR, Trevino JG. Human pancreatic cancer xenograsts recapitulate key aspects of cancer cachexia. Oncotarget. Jan 3;8(1):1177-1189, 2017
Delitto D, Judge SM, George TJ Jr, Sarosi GA, Thomas RM, Behrns KE, Hughes SJ, Judge AR, Trevino JG. A clinically applicable muscular index predicts long-term survival in resectable pancreatic cancer. Surgery. Dec 5, 2016
Ryder DJ, Judge SM, Beharry AW, Farnsworth CL, Silva JC and Judge AR. Identification of the Acetylation and Ubiquitin-Modified Proteome during the Progression of Skeletal Muscle Atrophy. PLoS ONE. Aug 24;10(8), 2015
Judge SM, Wu CL, Beharry AW, Roberts BM, Ferreira LF, Kandarian SC and Judge AR. Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia. BMC Cancer. Dec 24;14:997, 2014
Beharry AW, Sandesara PB, Roberts BM, Ferreira LF, Senf SM, and Judge AR. HDAC1 activates FoxO and is both sufficient and required for skeletal muscle atrophy. J Cell Sci. Apr 1;127(Pt 7):1441-53, 2014
Roberts BM, Frye GS, Ahn B, Ferreira LF and Judge AR. Cancer cachexia decreases specific Force and accelerates fatigue in limb muscle. Biochem Biophys Res Commun. Jun 7;435(3):488-92, 2013
Senf SM, Howard TM, Ahn B, Ferreira LF and Judge AR. Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration. PLoS ONE. Apr 23;8(4), 2013
Roberts BM, Ahn B, Smuder AJ, Al-Rajhi M, Gill LC, Beharry AW, Powers SK, Fuller DD, Ferreira LF, Judge AR. Diaphragm and ventilatory dysfunction during cancer cachexia. The FASEB J. Jul;27(7):2600-10, 2013
Reed SA, Sandesara PB, Senf SM and Judge AR. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. FASEB J. Mar; 26(3):987-1000, 2012
Senf SM, Sandesara PB, Reed SA, and Judge AR. Acetyltransferase Activity Differentially Regulates the Localization and Activity of the FOXO Homologues in Skeletal Muscle. Am J. Physiol. Cell Physiol. Jun;300(6):C1490-501, 2011
Reed SA, Senf SM, Cornwell EW, Kandarian SC, Judge AR. Inhibition of IkappaB kinase alpha (IKKα) or IKKbeta (IKKβ) plus forkhead box O (Foxo) abolishes skeletal muscle atrophy. Biochem Biophys Res Commun. Feb 18;405(3):491-6, 2011
Senf SM, Dodd SL and Judge AR. FOXO Signaling is Required for Disuse Muscle Atrophy and is Directly Regulated by Hsp70. Am J. Physiol. Cell Physiol. Jan;298(1):C38-45, 2010
Dodd SL, Hain BA, Senf SM and Judge AR. Hsp27 inhibits IKKb-induced NF-kB activity and skeletal muscle atrophy. FASEB J. Oct;23(10):3415-23, 2009
Senf SM, Dodd SL, McClung JM, Judge AR. Hsp70 overexpression inhibits NF-kB and Foxo3a transcriptional activities and prevents skeletal muscle atrophy. FASEB J. Nov;22(11):3836-45, 2008
Lab News & Pictures
Rachel Nosaka wins “Short Talk Prize” at the 3rd Cancer Cachexia Conference in Washington D.C., September 2016