Abdullah A. Osman, PhD
Department of Head and Neck Surgery, Division of Surgery
Present Title & Affiliation
Primary Appointment
Associate Professor, Department of Head and Neck Surgery - Research, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Assistant Professor, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX
Dual/Joint/Adjunct Appointment
Associate Professor, Department of Head and Neck Surgery - Research, The University of Texas MD Anderson Cancer Center, Houston, TX
Research Interests
The goal of my research is to 1) Stratify the Oral and Pharyngeal Squamous Cancer Based on p53 Mutational Status Using a Novel Mutation Ranking System and; 2) To target the mutant p53 in oral cancer and to understand if such mutation is associated with the tumor resistance to standard chemotherapy and radiation in patients with oral cancer. Oral cavity squamous cell carcinoma (OCSCC) causes significant morbidity and mortality here in the United States and worldwide, with over 250,000 diagnoses and 125,000 deaths annually. Mutation in TP53 gene is present in nearly 40-50% of head and neck squamous cell cancer, and has been associated with decreased survival in several large cohort studies. A majority of these mutations are missense mutations in the DNA-binding domain. As a result, the mutated p53 gene encodes a full-length protein incapable of transactivating its target genes. In addition to this loss of function, mutant p53 can have a dominant negative effect over the residual wild-type p53 and/or gain of function activity independent of the wild-type protein. Although p53 mutations provide cells with a selective growth advantage, such mutations burden them with significant checkpoint deficits; they cannot respond normally to chemo/or radiotherapy and enter mitosis and subsequently replicate their genome in the presence of DNA damage. To better understand the nature of the tumorigenic activity of mutant p53 in oral cancer, I have established stable knockout p53 isogenic cell lines by homologous recombination using recombinant adeno-associated virus (rAAV) strategy. I have also generated several stable null OSCC cell lines expressing low risk and high risk p53 point mutations. We believe that, these reagents are valuable research tools to examine the physiological role of mutant p53 both in vitro and in vivo in head and neck cancer. I am currently testing several HNSCC cell lines harboring different p53 mutants treated with cisplatin, docetaxel and erlotinib for their tumorigenic activity in vitro and in vivo in an orthotopic nude mouse model of oral cancer. These types of experiments would help us to determine the effects of chemo-radiosensitivity on cultured tumor cell lines expressing the specific mutations found similarly in the head and neck cancer patient population. By coupling clinical observations with laboratory data this project should specifically establish the utility of p53 mutation as a universal biomarker for HNSCC. Overall, the proposed study will help us to understand if there is a differential impact of p53 mutations on sensitivity to different antitumor drugs and radiation. If so, then the p53 mutation profile may be used to establish the usefulllness of p53 genotyping in clinical practice and personalize cancer therapy decisions.
Education & Training
Degree-Granting Education
| 2000 | UT Health Science Center at San Antonio, San Antonio, Texas, US, Biochemistry and Molecular Cell Biology, Ph.D |
| 1992 | King Saud University, Saudi, SA, Biochemistry, BS |
Postgraduate Training
| 2000-2003 | Postdoctoral, Molecular Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri |
Experience & Service
Faculty Academic Appointments
Assistant Professor, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 2015 - 2022
Research Instructor, Department of Head and Neck Surgery - Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 2010 - 2015
Assistant Professor, Department of Molecular and Cellular Oncology, King Fahad Medical City, Faculty of Medicine, Riyadh, 2007 - 2009
Research Instructor, Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, 2004 - 2007
Post-doctoral Fellow, Department of Molecular Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, 2000 - 2003
Teaching Assistant, Department of Biochemistry and Molecular Biology, Graduate School of Biomedical Sciences, San Antonio, TX, 1996 - 1997
Teaching Research Assistant, Department of Biochemistry and Molecular Biology, Northern Arizona University, Flagstaff, AZ, 1994 - 1995
Honors & Awards
| 2000 - 2003 | Post-doctoral Fellowship Award, National Institute of Health |
| 1998 - 1999 | Pre-doctoral Research Award, Howard Hughes Medical Institute |
Professional Memberships
Selected Presentations & Talks
National Presentations
- 2024. Early Career Talk. Invited. ARTNet Bi-annual PI meeting. Rockville, MD, US.
- 2013. MK-1775, a selective wee1 kinase inhibitor, overcomes cisplatin resistance associated with high risk TP53 mutation sin squamous cell carcinoma of the head and neck (oral presentation). Conference. AACR. Washington, DC, US.
- 2012. TP53 mutation status stratified by evolutionary gradient and structure model is a prognostic biomarker of overall survivalin head and neck squamous cell carinoma. Conference. AHNS. Toronto, CO, US.
International Presentations
- 2014. Sensitization of HPV+HNSCC to cytotoxic treatments by targeting the G2/M checkpoint with AZ-1775 to improve survival. Conference. AACR. Barcelona, ES.
- 2013. MK-1775, a selective wee1 kinase inhibitor, overcomes cisplatin resistance associated with high risk TP53 mutation sin squamous cell carcinoma of the head and neck (oral presentation). Conference. AACR. Washington, US.
- 2012. TP53 mutational status stratified by evolutionary gradient and structure model is a predictive biomarker of platinum based chemotherapy resistance in head and neck squamous cell carcinoma. Conference. AHNS. Toronto, CA.
Grant & Contract Support
| Date: | 2024 - 2026 |
| Title: | The University of Texas MD Anderson Cancer Center |
| Funding Source: | Stand Up to Cancer |
| Role: | Co-I |
| ID: | FP00018459_Res1 |
| Date: | 2022 - 2027 |
| Title: | The Houston Center for Acquired Resistance Research (H-CARR) – Project 2: Defining the Role of KEAP/NRF2 Signaling Dysregulation and Sensory Nerve Reprograming During Acquisition of Cisplatin Resistance and Metastasis in HNSCC |
| Funding Source: | NIH/NCI |
| Role: | Project Leader |
| ID: | 1U54CA274321-01 |
| Date: | 2021 - 2026 |
| Title: | Targeting Replication Stress and Homologous Recombination Repair Mechanisms in HPV-Positive and Negative Head and Neck Cancer |
| Funding Source: | NIH/NIDCR |
| Role: | PI |
| ID: | 5R01DE030104-03 |
| Date: | 2021 - 2026 |
| Title: | Progression and Metastasis of Oral Tongue Cancer |
| Funding Source: | NIH/NIDCR |
| Role: | Co-I |
| ID: | FP00011161 |
| Date: | 2019 - 2024 |
| Title: | Progression and Metastasis of Oral Tongue Cancer |
| Funding Source: | NIH/NIDCR |
| Role: | Co-I |
| ID: | 2R01DE014613-15A1 |
| Date: | 2019 - 2022 |
| Title: | Targeting DNA Damage Repair and Replication Stress for the Treatment of High-Risk Head and Neck Squamous Cell Carcinoma |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | PI |
| ID: | RP190118 |
| Date: | 2018 - 2023 |
| Title: | Novel Therapeutic Strategies to Target Replication Stress for the Treatment of High-risk HPV-driven HNSCC |
| Funding Source: | NIH/NIDCR |
| Role: | PI |
| ID: | 1R01DE026470-01A1 |
| Date: | 2018 - 2023 |
| Title: | MD Anderson Cancer Center Head & Neck SPORE – Project 3: Sensitization of Mutant TP53 Bearing Head and Neck Squamous Cell Carcinoma to Cytotoxic Treatments with COTI-2, a Novel 3rd Generation Thiosemicarbazone |
| Funding Source: | NIH/NCI |
| Role: | Co-I |
| ID: | 1P50CA217669-01A1 |
| Date: | 2016 - 2021 |
| Title: | Targeting Replication Stress through Wee-1 Kinase Inhibition for the Treatment of High Risk HPV-driven HNSCC |
| Funding Source: | NIH/NIDCR |
| Role: | PI |
| ID: | 1R01DE026470-01 |
| Date: | 2015 - 2018 |
| Title: | Sensitization of HPV+HNSCC to cytotoxic treatments G2/M checkpoint with AZ-1775 to improve survival |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-PI |
| ID: | RP150127 |
| Date: | 2014 - 2020 |
| Title: | Prediciting and overcoming chemoradioresistance in p53-mutant head and neck cancer |
| Funding Source: | NIH/NIDCR |
| Role: | Co-I |
| ID: | 5R01DE024601-04 |
| Date: | 2011 - 2014 |
| Title: | TP53 as a Biomarker to Personalize Chemotherapy for Patients with Head and Neck Cancer |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-I |
| ID: | RP120258 |
| Date: | 2010 - 2015 |
| Title: | Towards personalized cancer therapy: stratification of oral and pharyngeal cancer based on p53 mutational status |
| Funding Source: | Cancer Prevention & Research Institute of Texas (CPRIT) |
| Role: | Co-I |
| Date: | 2004 - 2007 |
| Title: | Development of Cholinergic Synapses in the Inner ear |
| Funding Source: | NIH/NIDCR |
| Role: | Co-I |
| ID: | NIH-NIDCD R01 DC004086 |
Selected Publications
Peer-Reviewed Articles
- Pifer PM, Yang L, Kumar M, Xie T, Frederick M, Hefner A, Beadle B, Molkentine D, Molkentine J, Dhawan A, Abdelhakiem M, Osman AA, Leibowitz BJ, Myers JN, Pickering CR, Sandulache VC, Heymach J, Skinner HD. FAK Drives Resistance to Therapy in HPV-Negative Head and Neck Cancer in a p53-Dependent Manner. Clin Cancer Res 30(1):187-197, 2024. e-Pub 2024. PMID: 37819945.
- Shi Y, Ren X, Cao S, Chen X, Yuan B, Brasil da Costa FH, Rodriguez Rosario AE, Corona A, Michikawa C, Veeramachaneni R, Osman AA, Xie T, Wang W, Sikora AG, Myers JN, Rangel R. TP53 gain-of-function mutation modulates the immunosuppressive microenvironment in non-HPV-associated oral squamous cell carcinoma. J Immunother Cancer 11(8), 2023. e-Pub 2023. PMID: 37604640.
- Yu W, Chen Y, Putluri N, Osman A, Coarfa C, Putluri V, Kamal AHM, Asmussen JK, Katsonis P, Myers JN, Lai SY, Lu W, Stephan CC, Powell RT, Johnson FM, Skinner HD, Kazi J, Ahmed KM, Hu L, Threet A, Meyer MD, Bankson JA, Wang T, Davis J, Parker KR, Harris MA, Baek ML, Echeverria GV, Qi X, Wang J, Frederick AI, Walsh AJ, Lichtarge O, Frederick MJ, Sandulache VC. Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state. Br J Cancer 128(11):2013-2024, 2023. e-Pub 2023. PMID: 37012319.
- Osman AA, Arslan E, Bartels M, Michikawa C, Lindemann A, Tomczak K, Yu W, Sandulache V, Ma W, Shen L, Wang J, Singh AK, Frederick MJ, Spencer ND, Kovacs J, Heffernan T, Symmans WF, Rai K, Myers JN. Dysregulation and Epigenetic Reprogramming of NRF2 Signaling Axis Promote Acquisition of Cisplatin Resistance and Metastasis in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 29(7):1344-1359, 2023. e-Pub 2023. PMID: 36689560.
- Shi Y, Xie T, Wang B, Wang R, Cai Y, Yuan B, Gleber-Netto FO, Tian X, Rodriguez-Rosario AE, Osman AA, Wang J, Pickering CR, Ren X, Sikora AG, Myers JN, Rangel R. Mutant p53 drives an immune cold tumor immune microenvironment in oral squamous cell carcinoma. Commun Biol 5(1):757, 2022. e-Pub 2022. PMID: 35902768.
- Michikawa C, Torres-Saavedra PA, Silver NL, Harari PM, Kies MS, Rosenthal DI, Le QT, Jordan RC, Duose DY, Mallampati S, Trivedi S, Luthra R, Wistuba II, Osman AA, Lichtarge O, Foote RL, Parvathaneni U, Hayes DN, Pickering CR, Myers JN. Evolutionary Action Score of TP53 Analysis in Pathologically High-Risk Human Papillomavirus-Negative Head and Neck Cancer From a Phase 2 Clinical Trial: NRG Oncology Radiation Therapy Oncology Group 0234. Adv Radiat Oncol 7(6):100989, 2022. e-Pub 2022. PMID: 36420184.
- Shi Y, Xie TX, Leach DG, Wang B, Young S, Osman AA, Sikora AG, Ren X, Hartgerink JD, Myers JN, Rangel R. Local Anti-PD-1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model. Cancer Prev Res (Phila) 14(8):767-778, 2021. e-Pub 2021. PMID: 34021022.
- Lindemann A, Patel AA, Tang L, Tanaka N, Gleber-Netto FO, Bartels MD, Wang L, McGrail DJ, Lin SY, Frank SJ, Frederick MJ, Myers JN, Osman AA. Combined Inhibition of Rad51 and Wee1 Enhances Cell Killing in HNSCC Through Induction of Apoptosis Associated With Excessive DNA Damage and Replication Stress. Mol Cancer Ther 20(7):1257-1269, 2021. e-Pub 2021. PMID: 33947685.
- Chari NS, Ivan C, Le X, Li J, Mijiti A, Patel AA, Osman AA, Peterson CB, Williams MD, Pickering CR, Caulin C, Myers JN, Calin GA, Lai SY. Disruption of TP63-miR-27a* feedback loop by mutant TP53 in head and neck cancer. J Natl Cancer Inst 112(3):266-277, 2020. e-Pub 2020. PMID: 31124563.
- Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 578(7795):449-454, 2020. e-Pub 2020. PMID: 32051587.
- Lindemann A, Patel AA, Silver NL, Tang L, Liu Z, Wang L, Tanaka N, Rao X, Takahashi H, Maduka NK, Zhao M, Chen TC, Liu W, Gao M, Wang J, Frank SJ, Hittelman WN, Mills GB, Myers JN, Osman AA. COTI-2, A Novel Thiosemicarbazone Derivative, Exhibits Antitumor Activity in HNSCC through p53-dependent and -independent Mechanisms. Clin Cancer Res 25(18):5650-5662, 2019. e-Pub 2019. PMID: 31308060.
- Tanaka N, Osman AA, Takahashi Y, Lindemann A, Patel AA, Zhao M, Takahashi H, Myers JN. Head and neck cancer organoids established by modification of the CTOS method can be used to predict in vivo drug sensitivity. Oral Oncol 87:49-57, 2018. e-Pub 2018. PMID: 30527243.
- Osman NA, Ibrahim HMA, Osman AA, Alnour RM, Gamal Eldin OA. Sero-prevalence of peste des petits ruminants virus antibodies in sheep and goats from the Sudan, 2016-2017. Virusdisease 29(4):531-536, 2018. e-Pub 2018. PMID: 30539057.
- Tanaka N, Zhao M, Tang L, Patel AA, Xi Q, Van HT, Takahashi H, Osman AA, Zhang J, Wang J, Myers JN, Zhou G. Gain-of-function mutant p53 promotes the oncogenic potential of head and neck squamous cell carcinoma cells by targeting the transcription factors FOXO3a and FOXM1. Oncogene 37(10):1279-1292, 2018. e-Pub 2018. PMID: 29269868.
- Tanaka N, Patel AA, Tang L, Silver NL, Lindemann A, Takahashi H, Jaksik R, Rao X, Kalu NN, Chen TC, Wang J, Frederick MJ, Johnson F, Gleber-Netto FO, Fu S, Kimmel M, Wang J, Hittelman WN, Pickering CR, Myers JN, Osman AA. Replication Stress Leading to Apoptosis within the S-phase Contributes to Synergism between Vorinostat and AZD1775 in HNSCC Harboring High-Risk TP53 Mutation. Clin Cancer Res 23(21):6541-6554, 2017. e-Pub 2017. PMID: 28790110.
- Tanaka N, Patel AA, Wang J, Frederick MJ, Kalu NN, Zhao M, Fitzgerald AL, Xie TX, Silver NL, Caulin C, Zhou G, Skinner HD, Johnson FM, Myers JN, Osman AA. Wee-1 Kinase Inhibition Sensitizes High-Risk HPV+ HNSCC to Apoptosis Accompanied by Downregulation of MCI-1 and XIAP Antiapoptotic Proteins. Clin Cancer Res 21(21):4831-44, 2015. e-Pub 2015. PMID: 26124202.
- Neskey DM, Osman AA, Ow TJ, Katsonis P, McDonald T, Hicks SC, Hsu TK, Pickering CR, Ward A, Patel A, Yordy JS, Skinner HD, Giri U, Sano D, Story MD, Beadle BM, El-Naggar AK, Kies MS, William WN, Caulin C, Frederick M, Kimmel M, Myers JN, Lichtarge O. Evolutionary action score of TP53 (EAp53) identifies high risk mutations associated with decreased survival and increased distant metastases in head and neck cancer. Cancer Res 75(7):1527-36, 2015. e-Pub 2015. PMID: 25634208.
- Osman AA, Neskey DM, Katsonis P, Patel AA, Ward AM, Hsu TK, Hicks SC, McDonald TO, Ow TJ, Alves MO, Pickering CR, Skinner HD, Zhao M, Sturgis EM, Kies MS, El-Naggar A, Perrone F, Licitra L, Bossi P, Kimmel M, Frederick MJ, Lichtarge O, Myers JN. Evolutionary action score of TP53 coding variants (EAp53) is predictive of platinum response in head and neck cancer patients. Cancer Res 75(7):1205-15, 2015. e-Pub 2015. PMID: 25691460.
- Fitzgerald AL, Osman AA, Xie TX, Patel A, Skinner H, Sandulache V, Myers JN. Reactive oxygen species and p21Waf1/Cip1 are both essential for p52-mediated senescence of head and neck cancer cells. Cell Death Dis 12;6(e1678), 2015. e-Pub 2015. PMID: 25766317.
- Osman AA, Monroe MM, Ortega Alves MV, Patel AA, Katsonis P, Fitzgerald AL, Neskey DM, Frederick MJ, Woo SH, Caulin C, Hsu TK, McDonald TO, Kimmel M, Meyn RE, Lichtarge O, Myers JN. Wee-1 kinase inhibition overcomes cisplatin resistance associated with high-risk TP53 mutations in head and neck cancer through mitotic arrest followed by senescense. Mol Cancer Ther 14(2):608-19, 2015. e-Pub 2015. PMID: 25504633.
- Zhou G, Wang J, Zhao M, Xie TX, Tanaka N, Sano D, Patel AA, Ward AM, Sandulache VC, Jasser SA, Skinner HD, Fitzgerald AL, Osman AA, Wei Y, Xia X, Songyang Z, Mills GB, Hung MC, Caulin C, Liang J, Myers JN. Gain-of-function mutant p53 promotes cell growth and cancer cell metabolism via inhibition of AMPK activation. Mol Cell 54(6):960-74, 2014. e-Pub 2014. PMID: 24857548.
- Chuang HC, Yang LP, Fitzgerald AL, Osman A, Woo SH, Myers JN, Skinner HD. The p53-reactivating small molecule RITA induces senescence in head and neck cancer cells. PLoS One 9(8):e104821, 2014. e-Pub 2014. PMID: 25119136.
- Gadhikar MA, Sciuto MR, Alves MV, Pickering CR, Osman AA, Neskey DM, Zhao M, Fitzgerald AL, Myers JN, Frederick MJ. Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functinal p53. Mol Cancer Ther 12(9):1860-73, 2013. e-Pub 2013. PMID: 23839309.
- Osman AA, Schrader AD, Hawkes AJ, Akil O, Bergeron A, Lustig LR, Simmons DD. Muscle-like nicotinic receptor accessory molecules in sensory hair cells of the inner ear. Mol Cell Neurosci 38(2):153-69, 2008. e-Pub 2008. PMID: 18420419.
- Bergeron AL, Schrader A, Yang D, Osman AA, Simmons DD. The final stage of cholinergic differentiation occurs below inner hair cells during development of the rodent cochlea. J Assoc Res Otolaryngol 6(4):401-15, 2005. e-Pub 2005. PMID: 16228856.
- Bao J, Lin H, Ouyang Y, Lei D, Osman AA, Kim TW, Mei L, Dai P, Ohlemiller KK, Ambronkkk RT. Activity-dependent transcription regulation of PSD-95 by neuregulin-1 and Eos. Nat Neurosci 7(11):1250-8, 2004. e-Pub 2004. PMID: 15494726.
- Osman AA, Saito M, Makepeace C, Permutt MA, Schlesinger P, Mueckler M. Wolframin expression induces novel channel activity in endoplasmic reticulum membranes and increases intracellular calcium. J Biol Chem 278(52):52755-62, 2003. e-Pub 2003. PMID: 14527944.
- Osman AA, Hancock J, Hunt DG, Ivy JL, Mandarino LJ. Exercise training increases ERK2 activity in skeletal muscle of obese Zucker rats. J Appl Physiol 90(2):454-60, 2001. e-Pub 2001. PMID: 11160042.
- Osman AA, Cusi K, Maezono K, Pendergrass M, Patti ME, Pratipanawatr T, DeFronzo RA, Kahn CR, Mandarino LJ. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase pathways of insulin receptor signaling in human muscle. J Clin Invest 105(3):311-20, 2001. e-Pub 2001. PMID: 10675357.
- Osman AA, Pendergrass M, Koval J, Maezono K, Mandarino LJ. Regulation of MAP kinase pathway activity in vivo in human skeletal muscle. Am J Physiol Endocrinol Metab 278(6):E992-9, 2000. e-Pub 2000. PMID: 10827000.
Review Articles
- Spiotto, MT, Taniguchi, C, Klopp, AH, Colbert, LE, Lin, SH, Wang, L, Frederick, MJ, Osman, AA, Pickering, CR, Frank, SJ. Biology of the Radio- and Chemo-Responsiveness in HPV Malignancies. Seminars in radiation oncology 31(4):274-285, 2021. e-Pub 2021. PMID: 34455983.
Abstracts
- Osman AA, Noriaki T, Patel AA, Wan J, Fitzgerald AL, Gadhikar MA, Skinner HD, Frederick MJ, Johnson F, Myers JN. Sensitization of HPV+HNSCC to cytotoxic treatments by targeting the G2/M checkpoint with AZ-1775 to improve survival. European Journal of Cancer 20(6):109, 2014. e-Pub 2014. PMID: 25691460.
- Osman AA, Ortega Alves M, Neskey DM, Monroe MM, Chuang H-C PA, Mason L, Meyn RE, Byers L, Katsonis P, Lichtarge O, Myers JN. MK-1775, a selective wee1 kinase inhibitor, overcomes cisplatin resistance associated with high risk TP53 mutations in squamous cell carcinoma of the head and neck. Proceedings of the American Association for Cancer Research 73(8):1136, 2013. e-Pub 2013.
Patient Reviews
CV information above last modified April 02, 2026