Boopathi E, Thangavel C. CDK4/6 inhibition protects normal cells against cancer therapy-induced damage. Transl Cancer Res. 2020 Feb; 9(2):405-408.

The main purpose of this commentary on myelopreservation with CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy by Weiss et al. (PMID: 31504118) is to discuss that CDK4/6 inhibitors are not only limited to suppression of the cancer cells growth but also functions as novel protectors for normal cells against cancer therapy induced toxicity. 

Javed E, Thangavel C, Frara N, Singh J, Mohanty I, Hypolite J, Birbe R, Braverman AS, Den RB, Rattan S, Zderic SA, Deshpande DA, Penn RB, Ruggieri MR Sr, Chacko S, Boopathi E. Increased expression of desmin and vimentin reduces bladder smooth muscle contractility via JNK2. FASEB J. 2020 Feb; 34(2): 2126-2146.

This study generated compelling evidence that JNK2 is a major effector of the BSM contractile dysfunction mediated by increased expression of intermediate filaments (IFs) proteins desmin and vimentin, strongly implicating an IFs/JNK2 dependent mechanism in BSM contractile dysfunction in bladder outlet obstruction.

Thangavel C, Gomes CM, Zderic SA, Javed E, Addya S, Singh J, Das S, Birbe R, Den RB, Rattan S, Deshpande DA, Penn RB, Chacko S, Boopathi E. NF-κB and GATA-Binding Factor 6 Repress Transcription of Caveolins in Bladder Smooth Muscle Hypertrophy. Am J Pathol. 2019 Apr;189(4):847-867.

This study demonstrates for the first time that GATA-6 and NF-κB repress caveolins genes transcription in human and murine BSM. This study details the mechanism of transcriptional repression of caveolins genes that occurs in BSM remodeling associated with obstructed bladder in patients with BPH.  

Thangavel C, Boopathi E, Liu Y, McNair C, Haber A, Perepelyuk M, Bhardwaj A, Addya S, Ertel A, Shoyele S, Birbe R, Salvino JM, Dicker AP, Knudsen KE, Den RB. Therapeutic Challenge with a CDK 4/6 Inhibitor Induces an RB-Dependent SMAC-Mediated Apoptotic Response in Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Mar 15; 24(6):1402-1414.

This study uncovers a novel function of RB activation to induce cellular apoptosis through therapeutic administration of a palbociclib and provides a rationale for the clinical evaluation of CDK 4/6 inhibitors in the treatment of patients with Non-Small Cell Lung Cancer (NSCLC).

Boopathi E, Hypolite JA, Zderic SA, Gomes CM, Malkowicz B, Liou HC, Wein AJ, Chacko S. GATA-6 and NF-κB activate CPI-17 gene transcription and regulate Ca²⁺ sensitization of smooth muscle contraction. Mol Cell Biol. 2013 Mar; 33(5): 1085-102.

In this study, we demonstrate that GATA-6 and NF-κB activate CPI-17 gene transcription and regulate Ca²⁺ sensitization of smooth muscle contraction. Our data provide insight into how GATA-6 and NF-κB mediate CPI-17 transcription, PKC-mediated signaling, and BSM remodeling associated with obstructed bladder in patients with BPH.