Habib Lab

Meet the Principal Investigator

Amyn Habib, M.D.

Amyn Habib, M.D.


I am a physician-scientist with a longstanding interest in signal transduction in cancer with a particular focus on glioblastoma. We are working on mechanisms of resistance to treatment targeted at receptor tyrosine kinase (RTK) pathways. In particular, I am interested in the early adaptive response triggered by RTK inhibition and therapeutic approaches to overcome this adaptive response. We are also working on mechanisms regulating invasion and proliferation in glioblastoma. In recent years, our work has become quite translational and we are actively pursuing clinical trials based on our basic research.

Meet the Lab Members

Gao Guo, Ph.D.

Gao Guo, Ph.D.

Assistant Professor
I received my Ph.D. in Biochemistry from Free University of Berlin in Germany.  I joined the Habib Lab as a postdoctoral fellow in 2014 and became an instructor in 2018. My research focuses on understanding the mechanism of resistance to EGFR inhibition in glioblastoma (GBM). I am also interested in oncogenic signaling in GBM invasion and proliferation.

Xiaoyao Yang, Ph.D.

Xiaoyao Yang, Ph.D.

Postdoctoral Researcher
Dr. Yang obtained his Ph.D. at the University of Science and Technology of China (USTC). His thesis focused on Radiotherapy and Radiation-induced bystander effects (RIBEs). The main work revealed the regulation of antioxidant transcription factor NRF2 in radiotherapy and RIBEs. In 2020, Dr. Yang joined the Department of Neurology, University of Texas Southwestern Medical Center for his postdoctoral training. His current work is trying to discover the mechanism of EGFR inhibitor resistance during chemotherapy for lung cancer and gliomas. Besides, he also works on the network of proteins that regulate invasion in glioblastoma. Dr. Yang has been committed to the biological research of cancer treatment, and he deeply hopes his study can benefit cancer patients.

Sansi Xing Ph.D.

Sansi Xing Ph.D.

Postdoctoral Researcher

Dr. Xing received her Ph.D. degree in Biochemistry at McMaster University. Her Ph.D. work focused on Tau alternative splicing regulation in neurodegenerative diseases and methods development for quantitative proteomics. Dr. Xing joined Habib Lab as a postdoctoral fellow in April 2023. Her current work is trying to decipher the novel function of EGFR signaling in the pathogenesis of glioblastoma (GBM). Besides, she also works on drug resistance to EGFR inhibition in lung cancer and GBM. She is very interested in translational medicine and her long-term goal is to develop personalized treatments for cancer patients.

Arifa Nayab

Arifa Nayab

Research Assistant
Born and raised in Chitral, Pakistan, I came to the U.S. for college in 2017. I received my B.A in Biology from St. Olaf College. I joined the Habib Lab in September 2021. My research interests include understanding the role of EGFR in various cancers. Outside of work, I enjoy cooking, playing table tennis, and watching movies with friends.

Harshitha Balla

Harshitha Balla

Medical Student

As a medical student at UT Southwestern, I am interested in the field of oncology and integrating it into my future career path. My research interests include cell signaling in tumor expression and navigating mechanisms of potential treatments. During the past year, I joined the Habib Lab to study EGFR signaling in glioblastomas. I will be focusing more specifically on how EGFR ligands promote invasion by regulating a specific set of extracellular proteins as part of my project for the Medical Student Summer Research Program. Outside of school and lab, I try to explore Dallas, which has become my home away from home, as an Austin native.


Our laboratory is interested in improving treatment for patients with glioblastoma (GBM) and other cancers. We work on understanding signal transduction pathways involved in the pathogenesis of cancer. Recent work has focused on investigating mechanisms of resistance to targeted treatment in GBM and lung cancer. We are also interested in mechanisms regulating invasion in GBM. 

    EGFR gene amplification and mutation is a signature lesion in GBM resulting in increased expression of EGFR wild type (EGFRwt) and oncogenic mutant forms of the EGFR such as EGFRvIII. Furthermore, experimental evidence suggests an important role for both EGFRvIII and EGFRwt in gliomagenesis. Thus, the EGFR is considered an important target in GBM. However, EGFR inhibition using tyrosine kinase inhibitors has not been successful in improving the survival of GBM patients. We have recently found that inhibition of the EGFR receptor in an experimental model of glioma resulted in the activation of an adaptive response that protected glioma cells from a loss of EGFR signaling.  Inhibition of this adaptive signaling response resulted in enhanced sensitivity to EGFR inhibition. Our initial studies suggested that a TNF-JNK-Axl-ERK signaling pathway mediates primary resistance to EGFR inhibition in GBM cells. In a subsequent study, we compared the efficacy of a combined EGFR plus TNF inhibition to temozolomide (TMZ), the standard of care treatment in GBM. We found that EGFR plus TNF inhibition is more effective compared to TMZ in large subsets of GBMs. 

    Aberrant EGFR signaling is common in non-small cell lung cancer (NSCLC). However, EGFR inhibition is effective only in tumors with EGFR-activating mutations. We have found that EGFR inhibition triggers adaptive responses in both EGFRwt and EGFR mutant NSCLC, and provided evidence that these adaptive responses play a role in mediating both primary as well as secondary resistance in NSCLC. Our initial studies have suggested that a TNF- NF-kB signaling pathway mediates resistance to EGFR inhibition in NSCLC and that combined inhibition of EGFR+TNF renders the majority of NSCLC sensitive to EGFR inhibition in a preclinical model, thus potentially expanding the reach and utility of EGFR inhibition in NSCLC greatly. More recently, we have found that EGFR inhibition triggers an adaptive response driven by co-optation of antiviral signaling pathways and induction of Type I IFNs that play a role in both primary and secondary resistance in NSCLC.

    Additionally, we have found that a broad targeting of the adaptive response to EGFR inhibition using glucocorticoids is substantially more effective compared to targeting of single pathways in overcoming resistance to EGFR inhibition in experimental models of lung cancer. A clinical trial to test this finding is ongoing.

    Aberrant EGFR signaling is widespread in cancer. However, EGFR signaling in cancer is still not well understood. When the EGFR is overexpressed it becomes tyrosine phosphorylated and constitutively active even in the absence of any exogenous ligand. While constitutive EGFR signaling has been reported, the downstream signals triggered by the EGFR in the absence of ligand are unclear. We demonstrated that constitutive and ligand induced EGFR signaling trigger distinct signaling networks. EGFR is a prime oncogene in GBM. We have recently demonstrated that EGFR ligands shift the role of EGFR from oncogene to tumor suppressor in EGFR amplified GBM. Thus, in EGFR amplified GBMs, ligand activation result in an unexpected suppression of invasion by upregulation of the cytoskeletal protein BIN3. We have identified BIN3 as a key signal that actively suppresses invasion in GBM. Furthermore, the tumor suppressive function of EGFR can be activated in GBM by using the drug tofactinib, which suppresses invasion in GBM. A clinical trial of tofactinib in recurrent GBM is ongoing.

    Featured Publications

    Guo G, Gong K, Beckley N, Zhang Y, Yang X, Chkheidze R, Hatanpaa KJ, Garzon-Muvdi T,  Koduru P, Nayab A, Jenks J, Sathe AA, Liu Y, Xing C, Wu SY, Chiang CM, Mukherjee B, Burma S, Wohlfeld B, Patel T, Mickey B, Abdullah K, Youssef M, Pan E, Gerber DE, Tian S, Sarkaria JN, McBrayer SK, Zhao D, and Habib AA.  EGFR ligand shifts the role of EGFR from oncogene to tumor suppressor in EGFR amplified GBM by suppressing invasion through BIN3 upregulation. Nat. Cell Biol. 2022 Aug . 24(8):1291-1305 doi: 10.1038/s41556-022-00962-4. Online ahead of print.  

    Gong K, Guo G, Beckley N, Zhang Y, Yang X, Gerber DE, Minna JD, Burma S, Zhao D, Akbay EA, and Habib AA. Comprehensive targeting of resistance to inhibition of RTK signaling pathways by using glucocorticoids. Nat. Commun.    2021 Dec 1;12(1):7014. doi: 10.1038/s41467-021-27276-7.

    Gong K, Guo G, Panchani N, Bender ME, Gerber DE, Minna JD, Fattah F, Gao B, Peyton M, Kernstine K, Mukherjee B, Burma S, Chiang CM, Zhang S, Sathe AA, Xing C, Dao KH, Zhao D, Akbay EA, and Habib AA.  EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer.  Nat. Cancer 2020 1, 394

    Guo G, Gong K, Puliyappadamba VT, Panchani N, Pan E, Mukherjee B, Damanwalla Z, Bharia S, Hatanpaa KJ, Gerber DE, Mickey BE, Patel TR, Sarkaria JN, Zhao D, Burma S, and Habib AA.  Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma.  Neuro Oncol. 2019 Dec 17;21(12):1529-1539. doi: 10.1093/neuonc/noz127.

    Gong K, Guo G, Gerber DE, Gao B, Peyton M, Huang C, Minna JD, Hatanpaa KJ, Kernstine K, Cai L, Xie Y, Zhu H, Fattah FJ, Zhang S, Takahashi M, Mukherjee B, Burma S, Dowell J, Dao K, Papadimitrakopoulou VA, Olivas V, Bivona TG, Zhao D, and Habib AA.   TNF-driven adaptive response mediates resistance to EGFR inhibition in lung cancer.  J Clin Invest.  2018 Jun 1;128(6):2500-2518. doi: 10.1172/JCI96148. Epub 2018 May 7.  PMID: 29613856

    Guo G, Gong K, Ali S, Ali N, Shallwani S, Hatanpaa KJ, Pan E, Mickey B, Burma S, Wang DH, Kesari S, Sarkaria JN, Zhao D, and Habib AA.  A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma.  Nat Neurosci. 2017 Aug;20(8):1074-1084. doi: 10.1038/nn.4584. Epub 2017 Jun 12.  PMID: 28604685

    Contact Us

    5323 Harry Hines Blvd.
    Dallas, TX 75390
    Phone: 214-645-6237
    Fax: 214-462-4518