Alexander Pertsemlidis, Ph.D.

Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs ( lncRNAs) are critical regulators of cell viability and drug response in both adult and pediatric cancers. Focusing on ncRNA-mediated cell-cell communication, my laboratory aims to develop non-invasive methods for the early detection of cancer and novel therapeutic agents. Our investigations are uncovering novel mechanisms of regulating intracellular signaling pathways — through the identification of ncRNAs that have direct therapeutic applications or through the elucidation of pathways that can be targeted through more traditional pharmacological interventions — and providing novel drug candidates for cancer treatment and novel, non-invasive biomarkers for predicting patient survival and personalizing treatment. While the high-throughput and high-content screens we employ have historically relied on reverse transfection of arrayed siRNAs, miRNA mimics, and miRNA and lncRNA inhibitors, the recent advances in genome editing now allow more precise dissection of the genes and networks responsible for changes in phenotype.

• Professional Background

  Education

  • 1995 - PhD - Biophysics - University of California
  • 1988 - MS - Cell and Molecular Biology - University of Michigan
  • 1987 - AB - Medieval History - Princeton University
  • Postdoctoral Training - Biochemistry, Computational Biology - UT Southwestern Medical Center
  • Postdoctoral Training - Genetics, Computational Biology - UT Southwestern Medical Center

  Appointments

  • 12/2016 - Present - Deputy Director, UTHSCSA Cancer Research Training Program - UT Health Science Center at San Antonio, Cellular & Structural Biology, San Antonio
  • 12/2012 - 01/2019 - Co-Leader, Cancer Biology Track - UT Health Science Center at San AntonioSan Antonio
  • 09/2011 - Present - Principal Investigator - UT Health Science Center at San Antonio, Greehey Children's Cancer Research InstituteSan Antonio
  • 09/2011 - Present - Associate Professor with Tenure - UT Health Science Center at San Antonio, Pediatrics, San Antonio

• Instruction & Training

  • 10/2016 - Present, CSBL5077 Scientific Writing, UT Health Science Center at San Antonio
  • 03/2014 - Present, CSAT6095 Analysis and Visualization of Genomic Data (formerly Functional Genomic Data Analysis), Medical College of Georgia at Augusta University
  • 07/2012 - Present, Programs to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE), Medical College of Georgia at Augusta University
  • 02/2012 - Present, CSAT5024 RNA Biology & Genomics, UT Health Science Center at San Antonio

• Research & Grants

  Pediatric Cancer, Lung Cancer, ncRNA/mRNA, RNA Biology, Computational Biology, Cancer Biology, High-content Screening, High-throughput Screening, Animal Models

  Experimental and Developmental Therapeutics Program 

  Research profile

  Grants

  Federal

  Funding Agency Department of Defense Title Identifying biomarkers of metastasis through biosynthetic tagging Status Active Period 9/2019 - 8/2020 Role Principal Investigator Grant Detail Cell lines derived from metastatic and non-metastatic models of murine lung adenocarcinoma will be stably transfected to express the UPRT enzyme and injected into syngeneic mice to induce tumor formation. The mice will be fed a diet supplemented with 4TU. Since the tumor cells express UPRT, they will synthesize TU-tagged miRNAs, while host cells, which do not express UPRT, will not. Any miRNAs that the tumor releases into the blood or adjacent tissue will also be TU-tagged. Separation of the miRNAs present in tumor, normal adjacent tissue and serum into labeled and unlabeled fractions followed by small RNA sequencing then enables the controlled comparison of the profile of miRNAs released into the blood specifically by the tumor relative to the profile of miRNAs from the host. We will use this approach to identify miRNA biomarkers of metastasis and to design therapeutic interventions based on reversing the changes in miRNA expression in the target cells. 

  Private

  Funding Agency The William and Ella Owens Medical Research Foundation Title Identifying microRNA biomarkers by tissue of origin Status Active Period 1/2016 - 07/2020 Role Principal Investigator Grant Detail Our studies are designed to provide the foundation for a comprehensive determination of the microRNA species that are transferred between cancer cells and normal cells, rigorous characterization of the rate, range and routes of transfer, and evaluation of the therapeutic potential of manipulating their intracellular levels in in vitro and in vivo models.

  Funding Agency William and Ella Owens Medical Research Foundation Title Hypoxis-derived treatment for advanced lung cancer (Kerwin, PI) Status Active Period 1/2016 - 12/2020 Role Co-Principal Investigator Grant Detail To identify the molecular mechanisms of action of rooperol in lung cancer cell lines, design and synthesize analogs and pro-drugs to improve its biological properties, and evaluate analogs to identify potential lead clinical candidate(s).

  Funding Agency William and Ella Owens Medical Research Foundation Title Identifying microRNA biomarkers by tissue of origin Status Complete Period 1/2016 - 12/2017 Role Principal Investigator Grant Detail To distinguish serum miRNAs by tumor/host origin in mouse models of lung adenocarcinoma by using a protozoan enzyme, uracil phosphoribosyltransferase (UPRT), to biosynthetically label newly synthesized miRNAs.

  State

  Funding Agency Cancer Prevention & Research Institute of Texas (CPRIT) Title UTHSCSA Cancer Research Training Program Status Active Period 12/2016 - 11/2021 Role Co-Principal Investigator Grant Detail This Research Training Award (RTA) provides support for predoctoral and postdoctoral (post-residency MD fellowship and basic science PhD) trainees as well as undergraduate students (summer research internship program) to receive training in cancer research. The overall goal is for trainees to be exposed to all aspects of cancer research (basic, translational and clinical) so that they will have a strong appreciation of, and progress on to independent and productive careers in cancer research. This is a continuation of two earlier RTAs (RP101491, 07/13/10 - 02/28/14; RP140105, 03/01/14 - 02/28/17).

  Funding Agency IIMS/CTSA/UTSA/GCCRI Title Elucidating how chromosome 21 protects against neuroblastoma occurrence Status Active Period 12/2014 - 11/2018 Role Principal Investigator Grant Detail To evaluate the effect of chr 21 trisomy on tumor cell growth rate in a neuroblastoma cell line model established from isogenic chr 21 disomy/trisomy iPS cells.

  Funding Agency Greehey Children's Cancer Research Institute Title Developing better controls for high-throughput screens Status Active Period 5/2017 - 4/2019 Role Principal Investigator Grant Detail We hypothesize that a pooled approach for negative control oligos can outperform commercially available miRNA mimic control, miRNA inhibitor control and RNAi control oligos, minimizing the deleterious effects associated with single oligo design while retaining the desirable properties of a control (same chemistry, same sequence composition).

• Publications

  Yu X, Zhang Y, Wu B, Kurie JM, Pertsemlidis A. The miR-195 axis regulates chemoresistance through TUBB and lung cancer progression through BIRC5. Molecular Therapy – Oncolytics 2019;14:288-298.

  Zhao Z, Partridge V, Sousares M,, Shelton SD, Holland CL, Pertsemlidis A, Du L. microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi PLoS ONE 2018;13(12).

  Li Y, Nowak C, Withers D, Pertsemlidis A, Bleris L. CRISPR-based editing reveals edge-specific effects in biological networks The CRISPR Journal 2018;:286-293.

  Du L, Zhao Z, Suraokar M, Shelton SS, Ma X, Hsiao TH, Minna JD, Wistuba II, Pertsemlidis A. LMO1 functions as an oncogene by regulating TTK expression and correlates with neuroendocrine differentiation of lung cancer Oncotarget 2018;9:29601-29618.

  Yu X, Zhang Y, Ma X, Pertsemlidis A. miR-195 potentiates the efficacy of microtubule-targeting agents in non-small cell lung cancer Cancer Letters 2018;427:85-93.

  Yu X, Ma Z, Zhang Y, Zhao Z, Du L, Pertsemlidis A. miR-195 targets cyclin D3 and survivin to modulate the tumorigenesis of non-small cell lung cancer Cell Death & Disease 2018;9(2).

  Lin J, Zandi R, Shao R P, Gu J, Ye Y, Wang J, Zhao Y, Pertsemlidis A, Wu X, Roth J A, Ji L. A miR-SNP biomarker linked to an increased lung cancer survival by miRNA-mediated down-regulation of FZD4 expression and Wnt signaling Scientific Reports 2017;7(9029).

  Zhao Z, Ma X, Li M, Sung D, Zhang M, Losiewicz MD, Chen Y, Pertsemlidis A, Yu X, Liu Y, Du L. A combined gene expression and functional study in neuroblastoma cell lines reveals the crosstalk between N-Myc and differentiation-inducing microRNAs in neuroblastoma Oncotarget 2016;7(48):79372-79387.

  Henry S, Kidner R, Reisenauer MR, Magedov IV, Kiss R, Mathieu V, Lefranc F, Dasari R, Evidente A, Yu X, Ma X, Pertsemlidis A, Cencic R, Pelletier J, Cavazos DA, Brenner AJ, Aksenov AV, Rogelj S, Kornienko A, Frolova LV. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells European Journal of Medicinal Chemistry 2016;120:313-328.

  Liu L, Pertsemlidis A, Ding LH, Story MD, Steinberg MH, Sebastiani P, Hoppe C, Ballas SK, Pace BS. A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease Experimental Biology and Medicine (Maywood) 2016;241(7):706-718.

  Zhao Z, Ma X, Sung D, Li M, Kosti A, Lin G, Chen Y, Pertsemlidis A, Hsiao TH, Du L. microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest RNA Biology 2015;12(5):538-554.

  Masi M, Frolova L, Yu X, Mathieu V, Cimmino A, De Carvalho A, Kiss R, Rogelj S, Pertsemlidis A, Kornienko A, Evidente A. Jonquailine, a new pretazettine-type alkaloid isolated from Narcissus jonquilla quail, with activity against drug-resistant cancer Fitoterapia 2015;102:41-48.

  Borkowski R, Du L, Zhao Z, Kosti AK, Yang CR, Suraokar M, Wistuba II, Gazdar AF, Minna JD, White MA, Pertsemlidis A. Genetic mutation of p53 and suppression of the miR-17∼92 cluster are synthetic lethal in non-small cell lung cancer due to upregulation of vitamin D signaling Cancer Research 2015;75(4):666-675.

  Vaisnav M, Xing C, Ku H-C, Hwang D, Stojadinovic S, Pertsemlidis A, Abrams JM. Genome-wide association analysis of radiation resistance in Drosophila melanogaster PLoS ONE 2014;9(8):104858-104858.

  Du L, Zhao Z, Ma X, Hsiao TH, Chen Y, Young E, Suraokar M, Wistuba I, Minna JD, Pertsemlidis A. miR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung cancer Oncogene 2014;33(34):4307-4315.

  Zhao Z, Ma, Xiuye, Hsiao, Tzu-Hung, Lin, Gregory, Kosti, Adam, Yu, Xiaojie, Suresh, Uthra, Chen Y, Tomlinson GE, Pertsemlidis A, Du L. A high-content morphological screen identifies novel microRNAs that regulate neuroblastoma cell differentiation OncoTarget 2014;15;5(9):2499-2512.

  Ahn, YH, Gibbons D, Chakravarti D, Creighton CJ, Rizvi Z, Adams H, Pertsemlidis A, Gregory P, Wright J, Goodall G, Flores E, Kurie J. Zeb1 drives prometastatic actin cytoskeletal remodeling by down-regulating miR-34a expression Journal of Clinical Investigation 2012;:3170-3183.

  Du L, Subauste MC, DeSevo C, Borkowski R, Baker M, Schageman JJ, Greer RM, Yang CR, Suraokar M, Wistuba II, Gazdar AF, Minna JD, Pertsemlidis A. miR-337-3p and its targets STAT3 and RAP1A modulate paclitaxel sensitivity in non-small cell lung cancers PLoS ONE 2012;7(6):e39167-e39167.

  Du L, Schageman JJ, Girard L, Hammond SM, Minna JD, Gazdar AF, Pertsemlidis A. MicroRNA expression distinguishes SCLC from NSCLC lung tumor cells and suggests a possible pathological relationship between SCLCs and NSCLCs J Exp Clin Cancer Res 2010;29:75-75.

  Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, Kurie JM. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression Genes Dev 2009;23(18):2140-2151.