Alexander Pertsemlidis, PhD

  • Rank: Associate Professor
  • Department: Pediatrics
  • Office: 3.100.22
  • Location: Greehey CCRI
  • Tel: 1.210.562.9062


Our research interests integrate computational biology, cancer biology and genetics. We study regulatory RNA molecules called non-coding RNAs (called that because they do not code for proteins), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), and how they regulate cancer cell growth and response to anti-cancer drugs.


Neuroblastoma –

Neuroblastoma is the most common extracranial solid tumor in childhood. The majority of children over 1 year of age present with disseminated metastases – these are aggressive, drug resistant and generally incurable. Treated with chemotherapy, surgery, radiation therapy, and/or stem cell transplantation, these children typically experience rapid recurrence of a more aggressive neuroblastoma. This demands the development of novel and more effective therapeutic approaches.


Our beliefs:

  • nature has already developed elegant but non-obvious solutions to most problem facing modern medicine,
  • there may be many different solutions to  the same problem, and
  • things that look the same at the tissue  level may look very different at the molecular level.



  • develop sensitive, non-invasive methods for early cancer detection, and
  • identify new drugs targeting specific adult and pediatric cancer subtypes, either directly or in combination with traditional therapeutic agents.



  • ncRNA regulation of cell viability and drug response in neuroblastoma
  • Trisomy 21 and protection against neuroblastoma
  • Therapeutic miRNAs in combination with conventional chemotherapy
  • Molecular sensors for detecting cancer at the single-cell Level
  • Separating tumor and host miRNAs through TU-tagging
  • Therapeutic regulation of the PI3K and Wnt signaling pathways



  • miRNA, lncRNA and mRNA expression signatures of cancer cells and normal cells,
  • interaction networks between miRNAs, lncRNAs and mRNAs,
  • ncRNAs and their regulatory targets characterized in vitro, in vivo and in silico,
  • functional relationships between ncRNAs and disease, and
  • candidate biomarkers, therapeutic targets and therapeutic agents.



Alexander Pertsemlidis, PhD, joined the Greehey Children’s Cancer Research Institute in August of 2011 with major faculty responsibilities as a Principal Investigator in the areas of Cancer Genetics, Experimental Therapeutics and Molecular Oncogenesis and Associate Professor in the Departments of Pediatrics and Cellular and Structural Biology. He received his doctoral degree from the University of California, Berkeley and completed two post-doctoral fellowships at UT Southwestern Medical Center, Dallas, Texas.



My research program is driven by several core beliefs: (1) We believe that RNA is much more important than the central dogma of molecular biology implies; (2) We believe that adult and pediatric cancers are mutually informative and that we learn from studying one will tell us something useful about the other; and (3) We believe that non-coding RNAs, including short non-coding RNAs like microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), can be used both as therapeutic agents and as probes of therapeutically relevant pathways.

Overall, 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 developing personalized therapeutic regimens. These investigations have contributed to our understanding of ncRNA roles in and beyond cancer pathogenesis and have established a foundation on which we can build in several orthogonal directions. We are extending the work to study how ncRNAs influence cellular response to drugs with different mechanisms of action, how they mediate intracellular transport and inter-cellular communication, how RNAs made by tumor cells can be distinguished from those made by host cells, and how we can improve therapeutic delivery. Importantly, all of our projects integrate in silico, in vitro and in vivo approaches.



Non-coding RNA Biology
The major focus of my lab is on investigating roles of non-coding RNA regulation in cancer pathogenesis, specifically: (1) non-coding RNA regulation of cell viability, and (2) non-coding RNA regulation of drug response. The long term goals of these projects are the identification of ncRNAs for which serum expression is a biomarker of either the presence or progression of tumors or of the likely response of a tumor to drug treatment, and of ncRNA mimics or inhibitors that can be delivered as therapeutic agents. Both projects integrate in silico, in vitro and in vivo approaches.

Computational Biology
Given the steadily increasing use of high-throughput methods in biomedical research, modern biologists need to understand both how biological data is collected and how to express biological problems in terms of algorithms and data structures. I believe that students should combine combine wet-lab and dry-lab work in both their courses and research projects. Such interdisciplinary training in computational and systems biology is appropriate to how modern biomedical research is evolving.

Neuroblastoma (NB) is a tumor that originates from neural crest precursor cells. It is the most common cancer in infants and the most common extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. The disease is highly heterogeneous, and is stratified into low- and high-risk categories. The overall prognosis for those with high-risk or relapsed disease remains poor despite the standard therapies of surgery, radiation, and chemotherapy. Low-risk neuroblastoma, however, frequently shows spontaneous regression, mainly in tumors with a near triploid number of chromosomes. The dichotomy between low- and high-risk neuroblastoma also raises interesting questions: (1) What are the molecular differences between low-risk and high-risk NB that lead to spontaneous regression in the former? Is the presence of additional copies of chromosomes in low-risk NB a clue as to the molecular mechanisms underlying regression? (2) Can specific genes or ncRNAs be altered to selectively kill NB cells or improve response to drug?

Lung Cancer
Lung cancer is divided into two major groups. 15% of bronchogenic carcinomas are small cell lung carcinomas (SCLC). Untreated SCLC has the most aggressive clinical course of any type of pulmonary tumor, with median survival of only 2-4 months from diagnosis. SCLC is typically diagnosed only when the disease has already metastasized, beyond the point at which surgical or radio/chemotherapeutic intervention is likely to be of benefit. The other 85% of bronchogenic carcinomas are non-small cell lung carcinomas (NSCLC), which is made up of several histological subtypes, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma. NSCLC progresses relatively slowly, and is characterized by significant heterogeneity in its response to treatment. This dichotomy between NSCLC and SCLC raises interesting questions: (1) Are specific genes or non-coding RNAs differentially expressed between states or between extremes of a phenotype within a state, like drug response? (2) Can a phenotype like drug response be changed by altering intracellular levels of a gene or non-coding RNA? (3) Can one subtype be turned into the other? Is SCLC a state that can be turned off? A major molecular difference between NSCLC and SCLC is the expression of a neuroendocrine program in the latter, including markers such as CHGA, SYP and NCAM. Interestingly, some SCLC has lost its neuroendocrine program, and some NSCLC has gained a neuroendocrine program

Statistical Genetics
Development and application of statistical methods to test associations between genotype and phenotype and testing the conventional wisdom that common disease is explained by common variants. Power and sample size calculations, kinship calculation, and statistical tests for association.




Funding Agency National Institute on Aging/San Antonio Nathan Shock Center
Title microRNA expression and dissemination in the progression of Alzheimer’s Disease
Status Active Active
Period 01/01/2017-12/31/2017
Role Principal Investigator
Grant Detail To test the hypothesis that inter-cellular communication between glial cells and neurons, specifically mediated by transfer of miRNAs through gap junctions, contributes to the propagation of AD pathology through activation of gamma secretase and APP cleavage


Funding Agency bioAffinity Technologies
Title Developing a simple, non-invasive fluorescence-based assay for early lung cancer detectionrapy
Status Active Active
Period 07/01/2016-07/01/2018
Role Principal Investigator
Grant DetailTo develop an automated early lung cancer detection assay using microscopy and flow cytometry-based technology.

Funding Agency William and Ella Owens Medical Research Foundation
Title Identifying microRNA biomarkers by tissue of origin
Status Active Active
Period 01/01/2016-12/31/2017
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.

Funding Agency William and Ella Owens Medical Research Foundation
Title Hypoxis-derived treatment for advanced lung cancer
Status Active Active
Period 12/01/2015-11/30/2017
Role Co-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


Funding Agency Institute for Integration of Medicine and Science/CTSA
Title Elucidating how chromosome 21 protects against neuroblastoma occurrence.
Status Active Active
Period 12/01/2014-11/30/2017
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 Cancer Research Training Grant
Status Active Active
Period 05/01/2017-04/30/2019
Role Principal Investigator
Grant Detail To develop a pooled approach for negative control oligos that can outperform commercially available miRNA mimic control, miRNA inhibitor control and RNAi control oligos.

Funding Agency CPRIT (Cancer Prevention and Research Institute of Texas) RTA
Title Cancer Research Training Program
Status Active Active
Period 12/01/2016-11/30/2021
Role Co-PI and Deputy Director
Grant Detail To establish a program spanning spans pre- and postdoctoral as well as undergraduate education to train individuals in all aspects of cancer basic science, translational and clinical areas of research