Theresa A. Guise, M.D., FASBMR

OMB No. 0925-0001 and 0925-0002 (Rev. 03/2020 Approved Through 02/28/2023)

BIOGRAPHICAL SKETCH

NAME: Theresa A. Guise

eRA COMMONS USER NAME (credential, e.g., agency login):  TAG4NNIH

POSITION TITLE:  Professor and Chief, Section of Bone and Mineral Disorders

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

INSTITUTION AND LOCATION

DEGREE

Completion Date

FIELD OF STUDY

Gannon PA, Erie, PA

University of Pittsburgh, School of Medicine University of Pittsburgh, Heath Center

 University of Texas, Health Sciences Center

B.S.

M.D.
Internship-
Residency
Fellow

05/1981

05/1985
06/1986
06/1988
06/1992

Biology
Medicine
Internal Medicine

Endocrinology

1. Personal Statement: My qualifications to serve as an Other Significant Contributor to Dr. Sue-Hwa Lin’s Project 2 of this Prostate Cancer SPORE proposal include 1) physician scientist endocrinologist with over 28 years research & training experience in animal models and human disorders of musculoskeletal complications of cancer and cancer treatment and most recently, on metabolism; 2) career focus on bone metastases, musculoskeletal health in the cancer patient as well as normal bone remodeling; 3) consistent funding and publications in complications of breast and prostate cancer and its treatment; 3) laboratory research group using basic molecular techniques, in vivo animal models and human studies in osteolytic and osteoblastic bone metastases due to breast, prostate, lung cancer, myeloma and melanoma; 4) active research program in cell biology of osteoclasts and osteoblasts; 5) establishment of muscle physiology laboratory to study the role of the bone microenvironment on cancer associated muscle weakness (ref: Contribution to Science #3a); 6) new research program to link increased bone destruction to diabetes mellitus; 7) founder and leader of the Tumor Microenvironment Program at Indiana University Simon Cancer Center (IUSCC); 8) training/mentoring of 33 postdoctoral fellows (24 Ph.D. and 9 Resident/Clinical), 3 Ph.D. students, 8 junior faculty and 28 summer (high school (8), undergrad (2) and medical students (18)) over 25 years; 9) providing reagents and training to study bone metastases to investigators world-wide; 10) described components of a feed-forward cycle between tumor and bone which fuels tumor growth and promotes muscle weakness; 11) active clinical practice of musculoskeletal complications in cancer patients at IUSCC; 12) leadership roles in ASCI, ASBMR, IBMS as well as permanent NIH study section member and Chair of SBSR, and Chairperson-elect for the Tumor Microenvironment Steering Committee (AACR). 13) continuous NIH funding since 1992, NCI since 1996.

2. Positions and Honors

   1988-1989                    Clinical Instructor, Dept Medicine, University of Pittsburgh School of Medicine

   1992-1998                    Assistant Professor, University of Texas Health Science Center/San Antonio, Dept Medicine, Div Endocrinology & Metabolism, San Antonio, TX

   1998-2002                    Associate Professor w/Tenure, University of Texas Health Science Center/San Antonio, Dept Medicine, Div Endocrinology & Metabolism, San Antonio, TX

   2001-2002                    Zachry Chair for Translational Research, Cancer Therapy & Research Center’s Institute for Drug Development, San Antonio Cancer Institute, San Antonio, TX

   2001-2002                    Associate Professor (with tenure), University of Texas Health Science Center/San Antonio, Dept Molecular Medicine, San Antonio, TX

   2002-2009       Gerald D. Aurbach Professor of Endocrinology, Professor, Medicine (tenure) & Orthopaedics, Div Endocrinology, Mellon Investigator, Univ. of Virginia, Charlottesville, VA

   2009-2020       Jerry and Peg Throgmartin Professor of Oncology, Professor of Medicine (with tenure), Div Endocrinology, Professor of Pharmacology, Indiana University, Indianapolis, IN

   Sept. 2020       Professor and Chief, Section of Bone and Mineral Disorders, Endocrine, Neoplasia and Hormonal Disorders; CPRIT Scholar, Univ of Texas MD Anderson Cancer Center, Houston, TX

   Sept. 2020       Co-Director, Rolanette and Berdon Lawrence Bone Disease Program of Texas

Honors/Awards: National Research Service Award, NIH (1991); Clinical Investigator Award, NIH (1992); New Investigator Award, US Army (1992); FIRST Award, NIH (1996); Outstanding Investigator Award, International Bone & Calcium Institute (1998); Fuller Albright Award, American Society Bone & Mineral Research (1999); Young Investigator Award, Advances in Mineral Metabolism (2000); Zachry Chair for Translational Research, Institute for Drug Development, University of Texas (2001); Gerald D. Aurbach Professor Endocrinology, Endowed Chair & Mellon Investigator, University of Virginia (2002); American Society Clinical Investigation (2004; elected secretary/treasurer 2006); Association of American Physicians (elected 2008); Outstanding Mentor, University of Virginia (2008); Donald Coffey Lecture, Society for Basic Urologic Research (2009); Legacy Laureate, University of Pittsburgh (2009); Scientific  Advisory Council, Komen Scholar, Susan G. Komen (2010-Present); Paula Stern Achievement Award, American Society for Bone and Mineral Research (2012); Philip S. Hench Distinguished Alumnus Award, University of Pittsburgh School of Medicine, Medical Alumni Association (2017); Presidential Address, Musculoskeletal Tumor Society of AAOS (2019); Avioli Memorial Lecture, ASBMR (2020); Cancer Prevention Research Institute of Texas (CPRIT) Scholar (2020); Stephen M. Krane Award, ASBMR (2020); Fellow, ASBMR (2020)

Professional Societies and Public Advisory Committees: Vice President, Cancer and Bone Society (2009); Board of Directors, Cancer and Bone Society (2008-Present); Program Leader of Tumor Biology and Microenvironment of the Indiana University Simon Cancer Center (2009-Presesnt); Member, Scientific Advisory Board, Institute of Molecular Medicine, Lisbon, Portugal (2007-2009); Skeletal Biology Structure & Regeneration Study Section, NIH (Chair: 2007-2009; Member: 2004-2007); Council Member and Secretary Treasurer, American Society for Clinical Investigation (2006-2010); Co-Chairman, 5th North American Skeletal Complications of Malignancy Meeting (2006); Member, Board of Directors, International Bone and Mineral Society (2005-2013); Co-Chairman, 6th North American Skeletal Complications of Malignancy Meeting (2005); Council Member, American Society for Bone and Mineral Research (2004-2007); Chairman, Education Committee, American Society for Bone and Mineral Research (2002-2005);  Member, Board of Directors, Advances in Mineral Metabolism (2001-2004); Co-Chairman, Program Committee for the 2002 Annual Meeting of the American Society for Bone and Mineral Research (2001-2002); Member, Paget Foundation Board of Directors (2000-2014); Chairman of the Board, Paget Foundation (2010-2014); Vice President, International Bone and Mineral Society (2011-2013), President, International Bone and Mineral Society (2013-2015); Tumor Microenvironment (TME) Steering Committee, AACR (2017-2022); Program Committee, AACR Annual Meeting, 2019; Tumor Microenvironment Steering Committee, Chairperson of the TME working group, AACR (2019-2022); Council member, Association of Osteobiology (2019-2022); President, Association of Osteobiology (2022-)

C: Contribution to Science (Guise publications http://www.ncbi.nlm.nih.gov/pubmed/?term=guise+t)

>160 publications; career citations >25,000; h-index 70 

1.Tumor-produced-produced factors in the bone microenvironment promote osteolytic bone destruction: Bone metastases cause pain and increase fracture risk. It was proposed for many years that tumor cells mediate bone destruction via osteoclasts: 1) tumors produce factors which stimulate osteoclast formation and activity; 2) histologic sections of bone metastases show tumor cells adjacent to bone-resorbing osteoclasts; 3) bisphosphonate inhibitors of bone resorption reduce bone destruction in bone metastases.  However, the exact mechanisms were unknown when I entered the field in 1989. I established a cancer cell line from a lung cancer bone metastases from the first patient I saw as an endocrinology fellow, discovered that it produced parathyroid hormone-related protein (PTHrP) and developed a mouse model of PTHrP-dependent hypercalcemia and bone metastases (Ref a). These initial studies led to the discovery of: 1) the central role for tumor–secreted PTHrP (Ref b), and its downstream mediator, receptor activator of NF kappa B ligand (RANKL) (Ref c), in osteolytic breast cancer bone metastases. The studies lead to clinical trials using humanized anti-PTHrP antibodies in patients with breast cancer bone metastases (Ref b) and were the first to show that tumor-produced factors stimulate osteoclastic bone resorption via induction of host osteoblast RANKL (Ref c). Anti-RANKL is now FDA-approved therapy for bone metastases, is widely used, and the most effective bone-targeted therapy for this disease. In collaboration with Yibin Kang and Joan Massagué, we investigated the molecular basis of osteolytic tumor metastasis to bone by selecting populations of cells from the human MDA-MB-231 breast cancer with high bone metastatic activity and profiling gene expression (Ref d). The bone metastasis phenotype was specifically linked to high expression of a set of genes encoding secreted and cell surface proteins not shared by sister populations highly metastatic to adrenal gland. Two of the bone metastasis genes, CTGF and IL-11, encode angiogenic and osteoclastogenic factors, while others encode factors responsible for homing of cancer to bone (CXCR4) and invasion (MMP1). All are regulated by TGF-β and act cooperatively to promote osteolysis. Thus, cancer metastasis to bone requires the expression of a specific gene sets, the proteins of which act at different stages in the metastatic cascade as well as on specific functions in bone. It is unlikely that any one tumor-produced factor could drive the formation of osteolytic bone metastases, but rather a central factor, which regulates many of these tumor-produced prometastatic genes. TGF-β is a central regulator of these genes, and links to the second significant scientific contribution. NIH grants: R01-CA69158 (years 1-5 on PTHrP; years 6-16 on TGFb)

1. Guise TA, Yoneda T, Yates AJP, Mundy GR.  The combined effect of tumor-produced parathyroid hormone-related peptide (PTHrP) and TGFa enhance hypercalcemia in vivo and bone resorption in vitro.  J Clin Endocrinol Metab 77(1):40-45, 1993.  PMID: 8325957.

2. Guise TA, Yin JJ, Taylor SD, Dallas M, Boyce BF, Yoneda T, Kumaga Y, Mundy GR. Evidence for a causal role of PTHrP in breast cancer mediated-osteolysis. J Clin Invest 98(7):1544-49, 1996.

3. Thomas, RJ, Guise, TA, Yin, JJ, Elliott, J, Horwood, NJ, Martin, TJ, Gillespie, M. Breast cancer cells interact with osteoblasts to support osteoclast formation.  Endocrinol. 140(10):4451-8.1999

4. Kang, Y, Siegel, PM, Shu, WP, Drobnjak, M, Käkönen, SM, Cordon-Cardo, C, Guise, TA, Massagué, J A multigenic program mediating breast cancer metastases  to bone. Cancer Cell 3(6):537-549. 2003

   2.TGFb in the bone microenvironment promotes osteolytic bone metastases: Our studies on tumor-produced PTHrP as a mediator of bone destruction in breast cancer osteolysis led us to test  the hypotheses that TGFb promotes osteolytic bone metastases by induction of tumor osteolytic factors, an idea that challenged existing dogma, since TGFb was known as a tumor suppressor. We showed that when MDA-MB-231 breast cancer was unresponsive to TGFb, tumor PTHrP production and bone metastases were blocked in vivo while enhanced TGFb signaling in MDA-MB-231 increased tumor PTHrP production and bone metastases (Ref a). These studies lead to development of TGFb inhibitors to treat bone metastases. Hypoxia is also a central regulator of pro-metastatic gene expression, so we asked whether hypoxia (via HIF-1α) and TGF-β signaling promote bone metastases independently or synergistically. Only vascular endothelial growth factor and the CXC chemokine receptor 4, of 16 genes tested, were additively increased by both TGFβ and hypoxia. We inhibited HIF-1α and TGF-β pathways in MDA-MB-231 breast cancer by shRNA and dominant negative receptor approaches. Inhibition of either pathway decreased bone metastasis, with no further effect of double blockade. In contrast, pharmacologic inhibitors of the pathways, which target both the tumor and the bone microenvironment decreased bone metastases more than either alone, with effects on bone to decrease osteoclastic bone resorption and increase osteoblast activity, in addition to effects on tumor cells.  Thus, hypoxia and TGF-β signaling in parallel drive tumor bone metastases and regulate a common set of tumor genes. In contrast, small molecule inhibitors, by acting on both tumor cells and the bone microenvironment, additively decrease tumor burden and improve bone. These studies suggest that inhibitors of HIF-1alpha and TGF-b may reduce bone metastases and increase survival (Ref b). NIH grants: R01-CA69158. Most recent data are consistent with a role for bone-derived TGF-β, increased in states of high bone destruction, such as that induced by complete estrogen deprivation, to promote tumor growth in bone and muscle weakness (Ref c).

1. Yin, JJ, Selander, KS, Chirgwin, JM, Dallas, M, Grubbs, BG, Wieser, R, Massagué, J, Mundy, GR, Guise TA TGF-b signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development.  J Clin Invest. 103(2):197. 1999

2. Dunn LK, Mohammad KS, Fournier PGJ, McKenna CR, Davis HW, Niewolna M, Peng XP, Chirgwin JM, Guise TA. Hypoxia and TGF-β Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment. PLoS One. 2009 Sep 3;4(9):e6896. PMID: 19727403; PMCID: PMC2731927.

3. Wright LE, Harhash AA, Kozlow WM, Waning DL, Regan JN, She Y, John SK, Murthy S, Niewolna M, Marks AR, Mohammad KS, Guise TA. Aromatase inhibitor-induced bone loss increases the progression of estrogen receptor-negative breast cancer in bone and exacerbates muscle weakness in vivo. Oncotarget. 2016 Dec 25. doi:10.18632/oncotarget.14139. PMID: 28039445, PMCID: PMC5352410.

3.Pathologic states associated with oxidation of RyR: bone metastases-associated muscle dysfunction (via TGFb) and impaired glucose metabolism: Cancer-associated muscle weakness is poorly understood and there is no effective treatment. Six mouse models of human osteolytic bone metastases [breast, lung, prostate] and multiple myeloma, exhibited impaired muscle function, implicating a role for the tumor-bone microenvironment. TGF-β, released from bone, upregulated NADPH oxidase 4 (Nox4) oxidizing skeletal muscle proteins, including the ryanodine receptor/calcium (Ca²⁺) release channel (RyR1). Oxidized RyR1 channels leaked Ca²⁺ reducing the signal required for muscle contraction. Inhibiting RyR1 leak, TGF-β signaling, TGF-β release from bone or Nox4 all improved muscle function. Humans with breast or lung cancer bone metastases also had oxidized skeletal muscle RyR1. Similarly, skeletal muscle weakness, increased Nox4 and oxidation of RyR1 were present in a mouse model of Camurati-Engelmann disease, a non-malignant bone disorder associated with increased TGF-b. Thus, TGF-b released from bone contributes to muscle weakness by decreasing Ca²⁺-induced muscle force production. (Ref a) These are the first data showing that bone can regulate muscle function in a systemic manner in the setting of increased bone destruction due to cancer or other high bone turnover states. R01-CA69158, U01-CA143057. In collaboration with Marks laboratory, oxidation of RyR2 impairs insulin secretion and glucose metabolism. (Ref. b).

1. Waning DL, Mohammad KS, Reiken S, Xie W, Andersson DC, John S, Chiechi A, Wright LE, Umanskaya A, Niewolna M, Trivedi T, Charkhzarrin S, Khatiwada P, Wronska A, Haynes A, Benassi MS, Witzmann FA, Zhen G, Wang X, Cao X, Roodman GD, Marks AR, Guise TA Excess TGFβ mediates muscle weakness associated with bone metastases in mice. Nature Medicine, 2015 Oct 12. doi: 10.1038/nm.3961. PMID: 26457758, PMCID: PMC4636436. featured on cover; News and Views

2. Santulli G, Pagano G, Sardu C, Xie W, Reiken S, Luca D’Ascia S, Cannone M, Marziliano N, Trimarco B, Guise TA, Lacampagne A, Marks AR Ryanodine receptor/calcium release channel regulates insulin release and glucose homeostasis. J Clin Invest, 2015 Apr 6. pii: 79273. doi: 10.1172/JCI79273. PMID:25844899, PMCID: PMC4463204

4.The TGFβ signaling regulator PMEPA1 suppresses prostate cancer metastases to bone: TGFβ regulates the expression of genes promoting breast cancer osteolysis, but little is known about TGFβ regulation of prostate cancer bone metastases. We showed that 1) TGFbR1 blockade reduced prostate cancer bone metastases; 2) TGFβ upregulates a set of genes associated with cancer invasiveness and bone metastases: the most upregulated gene was PMEPA1. In patients, PMEPA1 expression decreased in metastatic prostate cancer and low Pmepa1 correlated with decreased metastasis-free survival. Only membrane-anchored isoforms of PMEPA1 interacted with R-SMADs and ubiquitin ligases, blocking TGFβ signaling independently of the proteasome. Interrupting this negative feedback loop by PMEPA1 knockdown increased prometastatic gene expression and prostate cancer bone metastases in mice. Thus, in prostate cancer, TGFβ controls the expression of a pro-metastatic gene program similar to breast cancer, supporting the use of TGFβ inhibitors to treat prostate cancer bone metastases . PMEPA1 knock-down increased bone metastases. The identification of PMEPA1 as a major target of TGFβ and negative feedback regulator of TGFβ signaling suggests that PMEPA1 might be a useful prognostic marker of metastases to TGFβ-rich sites and predictor of metastasis-free survival. Enhancing membrane-bound PMEPA1 activity could be used as treatment strategy against prostate cancer bone metastases. (Ref a) R01-CA69158, U01-CA143057

1. Fournier PG, Juárez P, Jiang G, Clines GA, Niewolna M, Kim HS, Walton HW, Peng XH, Liu Y, Mohammad KS, Wells CD, Chirgwin JM, Guise TA. The TGF-β Signaling Regulator PMEPA1 Suppresses Prostate Cancer Metastases to Bone. Cancer Cell. 2015 May 12. pii: S1535-6108(15)00142-7. doi: 10.1016/j.ccell.2015.04.009. PMID: 25982816, PMCID: PMC4464909.

   5.Endothelins and the Wnt pathway in the pathophysiology of osteblastic bone metastases: Certain cancers, such as prostate and breast, stimulate abnormal bone formation as well as bone destruction, but there were no models in the 1990’s to define pathophysiology. These osteoblastic bone metastases are associated with similar morbidity as osteolytic bone metastases. We discovered the first mouse model of osteoblastic bone metastases (Ref a). Tumor-produced endothelin-1 (ET-1) caused the abnormal bone formation and the progression of bone metastases in a mouse model of osteoblastic bone metastases due to breast cancer (Ref a) by acting on the endothelin A receptor of the osteoblast (ETAR); later studies revealed that tumor-produced ET-1 mediated its effects by suppression of osteoblast DKK1 to activate the Wnt signaling pathway (Ref b).  The ETAR antagonist (atrasentan, Abbott) had no effect on tumor burden when the breast cancers were at sites outside of bone, such as in the primary site. These results confirmed the bone-specific nature of ETAR blockade and suggested that cancer treatment with ETAR antagonists would be beneficial for patients with bone metastases, but not for extraskeletal tumors. However the phase III study used overall survival as the primary endpoint and it was terminated early because interim analysis revealed that the primary endpoint (overall survival) would not be achieved. A subset analysis of the prostate cancer patients with bone metastases revealed that these patients had improved survival and delayed progression of bone metastases. Astrazeneca designed the appropriate phase III trial to treat men with prostate cancer patients with bone metastases with zibotentan in addition to the prostate cancer treatment. Zwibotetan reduced the progression of bone metastases (James et al., 2010 BJU Int. 106:966-73). However, as with atrasentan, a separate phase III trial of zibotentan as a general anticancer single agent failed. Collectively, these examples of dissecting the mechanisms for bone metastases as the basis for bone-targeted therapy of this devastating complication of cancer illustrate the innovativeness to challenge existing paradigms in cancer therapy. The studies on the role of ET-1 in the pathophysiology of osteoblastic bone metastases led to investigating the role for ET-1 in normal bone remodeling.  We generated a mouse with targeted deletion of ETAR in the osteoblast and showed that ET-1 was important for the maintenance of normal bone mass in the setting of androgen deficiency (Ref c). Thus, men with prostate cancer, treated with androgen deprivation and ETAR are at risk for bone loss.  NIH grants: P01CA40035, R01DK067333

1. Yin JJ, Mohammad KS, Käkönen SM, Harris S, Wu-Wong JR, Wessale J, Padley R, Garrett IR, Chirgwin JM, Guise,TA A causal role for endothelin-1 (ET-1) in the pathogenesis of osteoblastic bone metastases. Proc Natl Acad Sci USA. 2003 100(19):10954-9. PMID: 12941866 PMCID: PMC196909.

2. Clines GA, Mohammad KS, Bao Y, Stephens OW, Suva LJ, Shaughnessy JD Jr, Fox JW, Chirgwin JM, Guise TA. Dickkopf homolog 1 (Dkk1) mediates endothelin-1-stimulated new bone formation. Mol Endocrinol. 21(2):486-98, Feb 2007. Epub 2006 Oct 26.  PMID: 17068196, PMCID: PMC2013302

3. Clines GA, Mohammad KS, Grunda JM, Clines KL, Niewolna M, McKenna CR, McKibbin CR, Yanagisawa M, Suva LJ, Chirgwin JM, Guise TA. Regulation of postnatal trabecular bone formation by the osteoblast endothelin A receptor. J Bone Miner Res. 2011 Oct;26(10):2523-36. doi: 10.1002/jbmr.450. PMID: 21698666, PMCID: PMC3183222.

   D: Additional Information: Research Support and/or Scholastic Performance

Ongoing Research Support

R01CA206025 (Guise, contact PI; Territo, PI; Marks, PI)                                                                                         05/01/2016-04/30/2021

NIH/NCI

Title: (PQ#9) Targeting leaky ryanodine receptor (RyR2) to treat and prevent chemotherapy-associated cognitive dysfunction in patients with breast cancer

Goal: Determine if oxidation of RyR2 is associated with chemotherapy-induced cognitive dysfunction and whether rycal stabilization of RyR2 can prevent cognitive dysfunction.

BC171929 (Guise, PI)                                                                                                                                                                                                            9/01/2018 – 02/14/2022

Department of Defense Breast Cancer Research Program

Title: Role of Bone-derived TGF-beta on Glucose Metabolism in the Setting of Breast Cancer Bone Metastases

Goal: To determine if systemic effects of TGF-b derived from bone destruction induce hyperglycemia by oxidation of pancreatic RyR2 and suppressed insulin secretion.

RR190108 (Guise, PI)                                                                                                                                                                                                            06/01/2020-05/31/2025

Cancer Research Prevention Institute of Texas (CPRIT)

Title: Established Investigator Award

Metabolic complications of cancer and cancer treatment-induced bone destruction: Role of TGFβ-mediated oxidation.

Completed Research Support: (past 3 years)

P30CA082709-14 (Loehrer, PI; Guise, Co-Leader Tumor Microenvironment Program)

NIH/NCI Cancer Center Support Grant                                                                                                                                                          09/01/2019-08/31/2024

Overall:  Facilitate cancer research, education, care, and cancer control and prevention to accomplish the mission of reducing the incidence, morbidity, and mortality of cancer.

DOD BC150678 (Guise, PI; Thompson, Partner PI)                                                                                                             01/01/2016-01/31/2020

Title: Effect of Low-Magnitude Mechanical Signals on Breast Cancer Bone Metastases

Study low magnitude mechanical signals, alone or in combination with bisphosphonates, on bone and muscle loss resulting from aromatase inhibitors as well as breast cancer bone metastases

1 I01 BX002764-01A1 (Nakshatri; PI, Guise; Co-I)                                                        04/01/2015-03/31/2019

VA Merit Award  Title:  Mechanisms associated with systemic effects of cancer.

Study mechanisms of cancer cachexia and therapeutic modalities of miR-486, DMAPT and lospamimod.

BC134025 (Wright, PI; Guise, Mentor)                                                                                                                                                          07/15/2014 – 07/14/2018

DOD, Breast Cancer Research Program

Title: Musculoskeletal complications and bone metastases in breast cancer patients undergoing estrogen deprivation therapy.

The objective of this postdoctoral training grant is to evaluate the effects of aromatase inhibitor therapy on the musculoskeletal system in the context of breast cancer bone metastases.

U01 CA143057 (Guise; PI)                                                                                             04/07/2011 – 03/31/2017

NIH/NCI

Title:  Differential TGF-Beta Signaling in Bone Microenvironment:  Impact on Tumor Growth.

The goal is to compare bone cell-specific alterations in TGF-b signaling (host) with systemic inhibition of TGF-b (host & tumor) to target TGF-b to treat bone metastases.