Bawa-Khalfe Lab - University of Houston
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Center for Nuclear Receptors and Cell Signaling

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Bawa-Khalfe Lab

Tasneem Bawa-Khalfe, Ph.D.

Associate Professor
Department of Biology and Biochemistry

Office: SERC, 3010
Contact: tbawakha@central.uh.edu - 713-743-4288

The research focus of the Bawa-Khalfe laboratory is on how cancer cells exploit select post-translational modification (PTM) systems to drive cancer progression.

Figure

PTMs ensure the structural and functional diversity of a cell’s proteome. Most PTMs are dynamic and closely guarded via the activity of specific enzymes that conjugate or de-conjugate protein targets. Addition of the small ubiquitin-like modifier (SUMO) to a protein is a type of PTM that occur through a defined sequential process called SUMOylation. SUMOylation includes an SUMO E1 activating complex, the E2 conjugating enzyme Ubc9, and several E3 ligases (Fig. 1). Inversely, the isopeptidase activity of the SUMO proteases (SENP) reverts the substrate to an unmodified state or promotes deSUMOylation.

A large repertoire of cellular proteins is subject to SUMO PTM. SUMOylation affects the conjugated protein’s function, subcellular localization, and/or stability. Consistently, maintaining SUMO dynamics is important for normal cell physiology.

Figure

The onset of disease including cancer can alter the transcription, translation, and/or PTM of select components of the SUMO machinery. Naturally this disturbs the balance of SUMO modified to unmodified substrates (Fig. 2). An imbalance in the kinetics of SUMO PTM can initiate cancer development; for example, induction of SENP1 (SP1) elicits cancerous transformation of the normal mouse prostate gland (Bawa-Khalfe et. al. 2007). Recently, we reported alternative splicing of the SENP7 (SP7) gene product that is readily observed in human metastatic breast cancer samples (Bawa-Khalfe et. al. 2012). However, it is unclear how the loss of SUMO equilibrium supports the cancer transcriptome and an aggressive metastatic phenotype in breast cancer.

Figure

We are currently applying multiple genomic, epigenetic, and proteomic techniques to address this question; these techniques include chromatin immunoprecipitation (ChIP), ChIP-Seq, RNA-Seq, RNA immunoprecipitation (RIP), mass spectrometry, and in-vitro PTM analysis. The studies are performed at the level of the chromatin, monolayer cell cultures, 3D-acini tumor models (Fig. 3), and genetically engineered whole animal models. Hence, the laboratory’s research integrates results from a single cancer cell and more complex heterogeneous tumor microenvironments. This multipronged approach will provide a more accurate assessment of the therapeutic and/or diagnostic potential of SUMO and other PTM systems in aggressive cancers.

Tasneem Bawa-Khalfe

Tasneem Bawa-Khalfe, Ph.D.
Associate Professor

Department of Biology and Biochemistry
University of Houston
Houston, Texas 77204-5001

Office: SERC, 3010
Phone: 713-743-4288
tbawakha@central.uh.edu

Samaneh Karami

Samaneh Karami, Ph.D.
Postdoctoral Fellow

skarami@cougarnet.uh.edu

Ashfia F. Khan

Ashfia F. Khan, M.S.
Doctoral Student

akhan70@central.uh.edu

Anthony S. Peidl

Anthony S. Peidl
Doctoral Student

aspeidl@uh.edu

Kacie D. Waiters

Kacie D. Waiters
Doctoral Student

kdwaiter@central.uh.edu

Funmi Babajide

Funmi Babajide
Undergraduate Student Researcher

mobabaji@cougarnet.uh.edu

Previous Lab Members

  • Santosh Kumar, Ph.D., Previous Postdoctoral Fellow
  • Hariprasad Thangavel, Ph.D., Previous Postdoctoral Fellow
  • Shaymaa Bahnassy, Ph.D., Previous Doctoral Student
  • Henry Vo, Ph.D., Previous Doctoral Student (Co-Advisor)
  • Maram Qutinna, Ph.D., Previous Doctoral Student
  • Minji Chae, MS, Previous Masters Practicum Student
  • Hoang Lynna Nguyen, MS, Previous Masters Practicum Student
  • Bassell Alsad, MS, Previous Masters Practicum Student

Peer-Reviewed Articles (Chronological Order)

  1. Palacios AV, Acharya P, Peidl AS, Beck MR, Blanco E, Mishra A, Bawa-Khalfe T, Pakhrin SC. SumoPred-PLM: human SUMOylation and SUMO2/3 sites Prediction using Pre-trained Protein Language Model. NAR Genom Bioinform. 2024 Feb 7;6(1):lqae011. doi: 10.1093/nargab/lqae011.
  2. Khan AF, Karami S, Peidl AS, Waiters KD, Babajide MF, Bawa-Khalfe T. Androgen Receptor in Hormone Receptor-Positive Breast Cancer. International Journal of Molecular Sciences. 2024; 25(1):476. https://doi.org/10.3390/ijms25010476
  3. Quttina M, Waiters KD, Khan AF, Karami S, Peidl AS, Babajide MF, Pennington J, Merchant FA, Bawa-Khalfe T. Exosc9 Initiates SUMO-Dependent lncRNA TERRA Degradation to Impact Telomeric Integrity in Endocrine Therapy Insensitive Hormone Receptor-Positive Breast Cancer. Cells. 2023 Oct 20;12(20):2495.
  4. Premaratne A, Ho C, Basu S, Khan AF, Bawa-Khalfe T, Lin CY. Liver X Receptor Inverse Agonist GAC0001E5 Impedes Glutaminolysis and Disrupts Redox Homeostasis in Breast Cancer Cells. Biomolecules. 2023 Feb 10;13(2):345.
  5. Bahnassy S, Thangavel H, Quttina M, Khan, A, Dhanyalayam D, Ritho J, Karami S, Ren J, Bawa-Khalfe T. Constitutively Active Androgen Receptor Supports the Metastatic Phenotype of Endocrine-Resistant Hormone Receptor-Positive Breast Cancer. Cell Communication and Signaling. 18(1):154, 2020.
  6. Faria M, Karami S, Granados-Principal S, Dey P, Verma A, Choi DS, Elemento O, Bawa-Khalfe T, Cheng JC, Strom AM, Gustafsson JA. The ERβ4 variant induces Transformation of the Normal Breast Mammary Epithelial cell line MCF-10A; the ERβ variants ERβ2 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling. Oncotarget. 9 (15), 122201, 2018.
  7. Karami S, Lin F-M, Kumar S, Bahnassy S, Thangavel H, Quttina M, Li Y, Ren J, Bawa-Khalfe T. Novel SUMO-Protease SENP7S Regulates β-catenin Signaling and Mammary Epithelial Cell Transformation. Scientific Reports. 7:46477, 2017.
  8. Bawa-Khalfe T * Yang FM, Ritho J, Lin HK, Cheng J, Yeh ETH. SENP1 regulates PTEN stability to dictate prostate cancer development. Oncotarget, e-Pub 2016 Nov 11.
    *Co-corresponding Author
  9. Lin FM, Kumar S, Ren J, Karami S, Bahnassy S, Li Y, Zheng X, Wang J, Bawa-Khalfe T. SUMOylation of HP1α supports association with ncRNA to define responsiveness of breast cancer cells to chemotherapy. Oncotarget. e-Pub 2016 Apr 14.
  10. Huang C, Cheng J, Bawa-Khalfe T, Yao X, Chin YE, Yeh ET. SUMOylated ORC2 Recruits a Histone Demethylase to Regulate Centromeric Histone Modification and Genomic Stability. Cell Report. 2016 Apr 5;15(1):147-57. e-pub 2016 Mar 24.
  11. Dere R, Perkins AL, Bawa-Khalfe T, Jonasch D, Walker CL. β-catenin Links Loss of VHL to Increased AURKA Activity and Loss of Primary Cilia in RCC. Journal of the American Society of Nephrology, e-Pub 10/2014.
  12. Wang Q, Xia N, Li T, Xu Y, Zou Y, Zuo Y, Fan Q, Bawa-Khalfe T, Yeh ET, Cheng J. SUMO-specific protease 1 promotes prostate cancer progression and metastasis. Oncogene 32(19):2493-8, 5/2013. e-Pub 6/2012.
  13. Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF, Yeh ET. Identification of the Molecular Basis of Doxorubicin-Induced Cardiotoxicity. Nature Medicine 18(11):1639-42, 11/2012. e-Pub 10/2012.
  14. *Commentary: Sawyer DS. Antracyclines and Heart Failure. The New England Journal of Medicine. 368(12):1154-56, 3/2013.
  15. Bawa-Khalfe T *, Lu LS, Zuo Y, Huang C, Dere R, Lin FM, Yeh ET. Differential Expression of SUMO-Specific Protease 7 Variants Regulates Epithelial Mesenchymal Transition. Proceedings of the National Academy of Sciences U S A 109(43):17466-17471, 10/2012. e-Pub 10/2012.
    *Co-corresponding Author
  16. Bawa-Khalfe T, Cheng J, Lin SH, Ittmann MM, Yeh ET. SENP1 induces prostate intraepithelial neoplasia through multiple mechanisms. Journal of Biological Chemistry 285(33):25859-66, 8/2010. e-Pub 6/2010.
  17. Bawa-Khalfe T, Altememi GF, Mandyam CD, Schwarz LA, Eikenburg DC, Standifer KM. The presence of beta2-adrenoceptors sensitizes alpha2A-adrenoceptors to desensitization after chronic epinephrine treatment. BMC Pharmacology 7:16, 2007.
  18. Bawa-Khalfe T, Cheng J, Wang Z, Yeh ET. Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells. Journal of Biological Chemistry 52(282):37341-49, 2007. e-Pub 10/2007.
  19. Bawa T, Altememi GF, Eikenburg DC, Standifer KM. Desensitization of alpha 2A-adrenoceptor signalling by modest levels of adrenaline is facilitated by beta 2-adrenoceptor-dependent GRK3 up-regulation. British Journal of Pharmacology 138(5):921-31, 3/2003.

Invited Review Articles

  1. Bawa-Khalfe T, Yeh ET. SUMO losing balance: SUMO proteases disrupt SUMO homeostasis to facilitate cancer development and progression. Genes and Cancer 1(7): 748-758, 7/2010.
  2. Cheng J, Bawa T, Yeh ET. Role of desumoylation in the development of prostate cancer. Neoplasia 8(8):667-76, 2006.

Book Chapter

  1. Bawa-Khalfe T. Book Chapter Title: Isolation of In Vivo SUMOylated Chromatin-Bound Proteins. Methods in Molecular Biology: SUMO Methods and Protocols. Springer Science+Business, LLC, New York, New York, 205-216, 2016.
  2. Bawa-Khalfe T, Yeh ETH. The In Vivo Functions of Desumoylating Enzymes. In: Conjugation and Deconjugation of Ubiquitin Family Modifiers, Subcellular Biochemistry. 54. Ed(s) Groettrup M. Landes Bioscience and Springer Science, LLC: Austin, Texas, 170-183, 2010.