Daniel L. Kiss, PhD

The Kiss RNA lab currently focuses on two main areas of research.  Namely, developing novel RNA Therapeutics to treat and/or prevent human disease and performing experiments to understand fundamental mechanisms concerning the RNA molecular biology of mammalian cells. 

RNA Therapeutics:

As we are housed inside the Houston Methodist Research Institute (HMRI), the lab is committed to the translation of basic science discoveries to benefit human health. Shortly after the lab opened, we joined the HMRI’s RNA Therapeutics program and began working on our first therapeutic candidate, an RNA designed to counter genes driving oncogenic transformation and cell migration in certain breast cancers.  That work has earned Dr. Kiss a Career Development Award from The American Society for Gene and Cell Therapy.  https://www.asgct.org/research/news/october-2019/asgct-career-development-awards

COVID-19 updates:

We are applying our expertise and experience with designing and developing novel RNA therapeutics to the address the urgent need COVID-19 pandemic.  Our lab is providing all needed support as HMRI’s RNA Core develops an mRNA-based COVID-19 vaccine. https://www.houstonmethodist.org/-/media/pdf/pr/covid/HM-COVID-19-Vaccine-Research-Press-Release-03172020.ashx

The lab has also been developing a novel RNA vaccine for COVID-19.  We are still in the development stages and hope to test the vaccine candidates in animals in early 2021.  

In addition to providing support for the vaccine effort mentioned above, we are developing three candidate RNAs designed to treat active COVID-19 disease.  These RNA therapeutic candidates are designed to slow the course of the infection by interfering with the virus's replication machinery.  This work is in its early stages. 

RNA molecular biology:

The basic science research interests of the lab lie in the changes that occur in the RNA and molecular biology of cells when cellular stress responses converge to cause or exacerbate cardiovascular disease or cancer. I am building a two-pronged collaborative basic science group that leverages RNA molecular biology tools with both specialized and traditional RNA sequencing approaches combined with long-read sequencing to elucidate how these RNA-mediated changes occur.

Cytoplasmic RNA capping

The lab's work aims to determine the regulators that determine the conditions under which, and position(s) where, an RNA is capped in the cytoplasm. My lab uses both transcriptome-wide (microarrays, direct RNA sequencing, RNA-seq, and ribosome profiling) and targeted methods (qPCR, polysome gradients, etc.) to understand how cytoplasmic capping drives oncogenic transformation and stress responses linked to cardiovascular disease. Ultimately, I aim to uncover the evolutionary role of cytoplasmic RNA capping, and to decipher the mechanism(s) controlling the selection, generation, and regulation of capping sites, and to develop cytoplasmic capping-based drug responsiveness screens and/or RNA therapeutics.

The lab was recently awarded an R35 MIRA (5 years) grant from the National Institute of General Medical Sciences to study the molecular undepinnings of cytoplasmic capping and another grant from the American Heart Association (3 years) to better understand if cytoplasmic capping helps cells respond to stress in the cardiovascular system. 

FHIT

The other part of my lab focuses on how the FHIT tumor suppressor modulates the translation of the transcriptome in cancer. My work has shown that expression of the FHIT protein results in translational changes for several known cancer-linked mRNAs. Further, that translational regulation is often driven by the 5’ translation leader sequence of the mRNA. For my future FHIT research, I plan to build upon my published works by expanding ribosome profiling into FHIT negative patient tumor samples and by developing better cell lines where FHIT expression is more tightly regulated.

(updated 12-2-2020)