Swarnali Acharyya, PhD
The broad focus of our laboratory is exploring mechanisms of drug resistance and cancer metastasis. These are two major challenges that significantly limit anti-cancer therapy and claim millions of lives worldwide.
Metastasis originates from the Greek word meaning “change of place” and is the process by which cancer cells spread from their original site of origin to other parts of the body. Even if the primary tumor is diagnosed early, surgically removed or treated, cancer cells can remain in the body often culminating in aggressive metastatic disease, sometimes even after decades. Patients with metastatic disease often show poor response to conventional therapies and succumb to death.
The goal of our laboratory is to identify new mediators of metastasis and to develop strategies to sensitize these metastases to more effective therapies.
We utilize a combination of genetically engineered and xenograft mouse models to understand the process of metastasis.
We actively collaborate with clinical investigators to model the development and treatment of metastatic disease in preclinical models (see Figure B) and to validate our findings in patient-derived clinical samples.
We are particularly interested in investigating the tumor-microenvironment interactions that promote the growth and survival of metastasis and those that dictate therapeutic response.
Our primary focus lies on two types of solid tumors - metastatic breast cancer and lung cancer.
Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, Norton L, Brogi E and Massague J, A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell, 150(1), 165-178(2012). PMID 22770218
Oskarsson T, Acharyya S, Zhang XHF, Vanharanta S, Tavazoie SF, Morris PG, Downey RJ, Manova-Todorova K, Brogi E and Massague J. Breast cancer cells produce tenascin-C as a metastatic niche component to colonize the lungs. Nature Medicine, 17, 867-74 (2011). PMID 21706029
Acharyya S, Sharma SM, Cheng A, Ladner KJ, Wang H, He W, Ostrowski M, Huang TMH, Guttridge DC. TNF inhibits Notch-1 in skeletal muscle by Ezh2 and DNA methylation mediated repression: implications in Duchenne muscular dystrophy. PLoS One 5(8): e12479 (2010). PMID 20814569
Kim MY, Oskarsson T, Acharyya S, Nguyen DX, Zhang XH, Norton L and Massague J. Tumor self-seeding by circulating cancer cells. Cell, 24: 139(7):1315-26 (2009) PMID 20064377
Damrauer J*, Stadler ME*, Acharyya S*, Baldwin AS, Couch ME and Guttridge DC. Chemotherapy-induced muscle wasting: association with NF-kB and cancer cachexia. Basic Applied Myology. 18(5):139-148 (2008) *Contributed equally.
Bakkar N, Wang J, Ladner K, Wang H, Dahlman JM, Carathers M, Acharyya S, Rudnicki MA, Hollenbach AD and Guttridge DC. IKK/NF-kappaB regulates skeletal myogenesis via a signaling switch to inhibit differentiation and promote mitochondrial biogenesis. J. Cell Biol. Feb; 180(4):787-802. (2008) PMID 18299349
Gupta GP, Perk J, Acharyya S, de Candia P, Mittal V, Todorova-Manova K, Gerald WL, Brogi E, Benezra R and Massagué J. ID genes mediate tumor re-initiation during breast cancer metastasis. PNAS 104(49):19506-11 (2007) PMID 18048329
Wang H, Hertlein E, Bakkar N, Sun H, Acharyya S, Wang J and Guttridge DC. NF-kB regulation of YYI inhibits skeletal myogenesis through transcriptional silencing of myofibrillar genes. Mol. Cell. Biol. Jun; 27(12):4374-87. (2007). PMID 17438126
Acharyya S and Guttridge DC. Cancer Cachexia Signaling pathways continue to emerge yet much still points to the proteasome. Clin Cancer Res. Mar 1;13(5):1356-61. (2007). PMID 17332276
Acharyya S, Villalta SA, Bakkar N, Bupha-Intr T, Janssen PML, Carathers M, Karin M, Li ZW, Beg A, Ghosh S, Sahenk Z, Weinstein M, Gardner KL, Rafael-Fortney JA, Tidball JG, Baldwin AS and Guttridge DC. IKK/NF-kB Signaling Interplay in Macrophages and Myofibers Promotes Muscle Wasting in Duchenne Muscular Dystrophy. J Clin Invest, 117(4): 889-901. (2007). PMID 17380205
Acharyya S, Butchbach ME, Sahenk Z, Wang H, Saji M, Carathers M, Ringel MD, Skipworth RJ, Fearon KC, Hollingsworth MA, Muscarella P, Burghes AH, Rafael-Fortney JA, Guttridge DC. Dystrophin glycoprotein complex dysfunction: a regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell, 8(5): 421-32 (2005). PMID 16286249
Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S and Guttridge DC. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest, 114(3): 370-8 (2004). PMID 15286803