Aikseng Ooi, PhD

Assistant Professor
Department(s): 
Pharmacology & Toxicology

http://www.u.arizona.edu/~ooi/

The transcriptional and the metabolic programs of a cell are two fundamental sets of instructions that dictate the behavior of the cell, the functions performed by the cell, and how the cell responds to various stimuli. These two programs interact with one another and change in response to physiochemical stimuli, enabling the cell to restore cellular homeostasis. Permanent alteration to these cellular programs contributes to the development of various pathologic conditions. Our research focuses on characterizing the mechanisms by which these pathologic alterations arise. Computational analyses of omics data and computational modeling allow us to quantify pathological changes to these cellular programs and to predict the mechanisms by which those changes occur. The predictions made through the computational methods can then be tested using the tools of biochemistry and of molecular genetics. A mechanistic understanding of how pathologic alterations to the cellular transcriptional and the cellular metabolic programs occur is the key to disease management and therapeutic development.    

X1) Hereditary leiomyomatosis and renal cell cancer (HLRCC)

Hereditary leiomyomatosis and renal cell cancer (HLRCC), a hereditary cancer syndrome characterized by the variable development of skin leiomyomas, uterine fibroids, and type 2 papillary renal cell carcinoma (PRCC2), is caused by biallelic inactivation of the gene encoding the Kreb’s cycle enzyme fumarate hydratase (FH). The most immediate consequence of FH inactivation is the accumulation of intracellular fumarate, a thiol-reactive Kreb’s cycle’s metabolite that can form covalent adducts with reactive sulfhydryl groups of biomolecules. We have demonstrated that such covalent adducts are responsible for the sustained activation of the NRF2 (nuclear factor erythroid 2–like 2) transcription factor which thus alters cellular transcriptional programming. In addition, HLRCC-associated cancer cells exhibit a strong Warburg effect phenotype, a hallmark of cancer that is characterized by an increased reliance on glycolysis for energy production, increased fermentation of glucose into lactate, and decreased oxygen consumption. Our current research into this syndrome focuses on identifying the mechanisms by which HLRCC-associated cancer cells acquire the altered metabolic program (Warburg effect phenotype) and the proliferative signal (growth signal).

X2) Development of algorithms for the analysis of transcriptomic data

The cellular transcriptional program is a robust system that changes in response to various internal and external stimuli. As such, the transcriptomic data derived from a tissue carries the imprints of all perturbations endured by the tissue. These imprints can be accessed through the use of present-day genomic technologies (microarrays and RNA sequencing), which essentially take a snapshot of the transcriptome. The amount of information that could be deciphered from the transcriptomic data is very much dependent on the power of the algorithms employed to analyze it. We are interested in developing new computational algorithms and frameworks to decipher new information from newly generated as well as legacy transcriptomic data.

X3) Transcriptional and metabolic reprogramming in response to physiochemical stimuli

A living cell responds and adapts to physiochemical changes by altering its transcriptional and its metabolic programs. When a physiochemical change is acute, the alterations in those cellular programs help to restore cellular homeostasis. However, in conditions of chronic physiochemical changes such as a gene mutation or chronic exposure to environmental pollutants, the resulting cellular reprogramming can adversely affect cellular behavior and cause permanent cellular reprogramming. We are interested in identifying the mechanisms by which chronic physiochemical changes mediate permanent cellular reprogramming. By applying massive parallel sequencing (also known as the next-generation sequencing), we can identify changes at the genetic and epigenetic levels that are inflicted by a specific chronic physiochemical insult. Computational and in vitro cellular modeling will allow us to identify the mechanisms by which permanent reprogramming occurs.

Publications

1. The full-length clone of cucumber green mottle mosaic virus and its application as an expression system for Hepatitis B surface antigen.

Ooi A, Tan S, Mohamed R, Rahman NA, Othman RY.

Journal of biotechnology. 2006; 121(4):471-81.

Teoh PG, Ooi AS, AbuBakar S, Othman RY.

Journal of biomedicine & biotechnology. 2009; 2009:781712.

Tan FL, Ooi A, Huang D, Wong JC, Qian CN, et al.

International journal of cancer. Journal international du cancer. 2010; 126(10):2353-61.

Li XJ, Ong CK, Cao Y, Xiang YQ, Shao JY, et al.

Cancer research. 2011; 71(8):3162-72.

Ang MK, Ooi AS, Thike AA, Tan P, Zhang Z, et al.

Breast cancer research and treatment. 2011; 129(2):319-29.

Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, et al.

Cancer cell. 2011; 20(4):511-23.

Chong LY, Cheok PY, Tan WJ, Thike AA, Allen G, et al.

Breast cancer research and treatment. 2012; 132(1):143-51.

Ong CK, Subimerb C, Pairojkul C, Wongkham S, Cutcutache I, et al.

Nature genetics. 2012; 44(6):690-3.

11. Fumarate hydratase inactivation in renal tumors: HIF1α, NRF2, and "cryptic targets" of transcription factors.

Ooi A, Furge KA.

Chinese journal of cancer. 2012; 31(9):413-20.

Wondergem B, Zhang Z, Huang D, Ong CK, Koeman J, et al.

Cancer research. 2012; 72(17):4361-71.

Lee SY, Chao-Nan Q, Seng OA, Peiyi C, Bernice WH, et al.

Journal of translational medicine. 2012; 10:206.

Ooi A, Dykema K, Ansari A, Petillo D, Snider J, et al.

Cancer research. 2013; 73(7):2044-51.

Wong MH, Tan CS, Lee SC, Yong Y, Ooi AS, et al.

Familial cancer. 2014; 13(2):281-9.

Tao S, Wang S, Moghaddam SJ, Ooi A, Chapman E, et al.

Cancer research. 2014; 74(24):7430-41. NIHMSID: NIHMS638086

Cutcutache I, Suzuki Y, Tan IB, Ramgopal S, Zhang S, et al.

European urology. 2015.

 

Publications
Originally posted: July 1, 2014
Last updated: September 3, 2015
Want to update? Contact Webmaster
Share This