Dr. Dihua Yu
The University of Texas MD Anderson Cancer Center
Department of Molecular and Cellular Oncology
In the new era of personalized cancer therapy, several new challenges are emerging. Our research is focused on tackling these imposing challenges. First, we are dissecting mechanisms of resistance to targeted- and immuno- therapies, and designing counteracting strategies to help patients respond to anti-cancer therapies. Second, we are decoding cancer metastasis, especially brain metastasis, and designing effective therapies based on mechanistic understanding. Third, we are developing strategies of early detection, prevention, and intervention of cancer. We also study dysregulation of i) metabolism, ii) immune responses, iii) tumor microenvironment, and iv) epigenetic modifiers, and their roles in cancer progression, metastasis, and resistance to therapies. We use multidisciplinary approaches, e.g., 2D and three-dimensional (3D) cell culture models and various preclinical animal models, including cancer cell xenograft, patient-derived xenograft (PDX), transgenic, and knockout mouse model, as well as tissue and plasma specimens from patients.
A tutorial in my laboratory would offer training in critical thinking, teach key concept and knowledge in studying mechanisms of cancer metastasis and response to immunotherapy; provide experience in 3D cell culture and various co-cultures, various mouse models, various unbiased “-omics” approaches, bioinformatics, in vitro and in vivo immune cell functional analyses; in vitro and in vivo assays of metastases to the lungs, bones and brain, biomarker detection in human cancer specimens, assays for studying transformation phenotypes and basic techniques in gene regulation, molecular cloning, gene transfer, and CRISPR/Cas9-based gene editing and screening. We also emphasize training in scientific presentations.
A few potential rotation projects are:
- Testing the effect of nutrient supplements in enhancing response to immuno-therapies in animal models and studying underlying mechanisms.
- Investigating how metabolic dysregulation, and immuno-suppression of the brain microenvironment empower brain metastasis outgrowth.
- Testing the effect of various targeting agents in inhibition of brain metastasis in various animal models.
- Testing prevention of breast cancers by vaccination, low-dose immune checkpoint blockade, plus nutrient modulation.
A few recent papers from my team (First authors of 2 and 3 were GSBS students):
- Zhang S, Huang WC, Li P, Guo H, Poh SB, Brady SW, Xiong Y, Tseng LM, Li SH, Ding Z, Sahin A, Esteva FJ, Hortobagyi G, and Yu D. Combating Trastuzumab Resistance by Targeting Src, a Common Node Downstream of Multiple Resistance Pathways. Nature Medicine 17:461-9, 2011. PMCID: 3877934.
- Xu J, Acharya S, Sahin O, Zhang QL, Yao J, Wang H, Li P, Lowery FJ, Saito Y, Kuo WL, Ensor J, Sahin A, Hung MC, Zhang JD, Yu D. 14-3-3ζ turns TGF-β's function from tumor suppressor to metastasis promoter in breast cancer by contextual changes of Smad partners from p53 to Gli2. Cancer Cell, 27;177, 2015. PMCID: PMC4325275.
- Zhang L, Zhang S, Yao J, Lowery FJ, Huang W-C , Zhang C, Wang H, Palmieri D, Zhang Q, Cheerathodi M, McCarty JH, Huang S, Sahin AA, Aldape KD, Steeg PS, Yu D. Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature, 527(7576):100-4, 11/2015. PMCID: PMC4819404.
- Zhou Z, Li M, Zhang L, Zhao H, Sahin Ö, Chen J, Zhao JJ, Songyang Z, Yu D. Oncogenic kinase-induced PKM2 tyrosine 105 phosphorylation converts non-oncogenic PKM2 to a tumor promoter and induces cancer stem-like cells. Cancer Res 78(9):2248-2261, 5/2018. e-Pub 2/2018. PMCID: PMC5932213.