UTMB

Xiaodong Cheng, Ph.D.,
Professor

Faculty

Xiaodong Cheng, Ph.D.

About the Lab

The major research focus in our laboratory is function and regulation of protein kinases and small GTPases and their roles in cancers. Currently, there are three independent but closely related projects in the lab. The first two are related intracellular signaling mediated by cAMP. cAMP-dependent protein kinase (PKA) isoforms play different roles in regulating various cellular processes, such as cell growth and differentiation. The linkage between certain PKA isoforms and cancer has also been firmly established. However, the underlying biochemical and structural principles for isoform-specific PKA functions are not clearly understood. To bridge this gap in our understanding, we are investigating the structure and function of different PKA isoforms using biochemical, molecular and cellular approaches. Particularly, we will apply chemical-genetic and functional proteomic approaches to determine the cellularsubstrates of different PKA isoforms. Recently, a family of novel intracellular cAMP receptors, Exchange proteins directly activated by cAMP (Epac), has been discovered. The finding of a second intracellular cAMP receptor in addition to PKA suggests that some, or even the majority of cAMP actions described in the vast cAMP literature, do not act through the activation of PKA alone, as previously believed. Therefore, dissecting the functional roles of Epac in the overall cAMP-mediated intracellular signaling is another major emphasis of the lab. Finally, we are also conducting study of the molecular mechanism of ovarian cell transformation and tumorgenesis using a genetically defined ovarian cancer model and functional proteomics approaches.

Interview with Dr. Cheng

– by Anasuya Roychowdhury, 3rd year BSCB Student

Xiaodong comes across to me as one of the talented young scientists on campus. Being an ex-student of UTMB and a real gentleman, he shares a special position in the department too. Considering the fact that he graduated from UTMB, my utmost curiosity drove me to ask him about why he chose to come back to UTMB. “I never thought about coming back to my old place but then the environment of the department, the advantage of knowing many people around, and of course the multidisciplinary nature of the program attracted me”, replied Xiaodong. He initially began his career in biophysics, and later on moved onto seeking a bridge to broaden his research interest by involving research in signaling, cancer biology and drug development. He thinks that this can only be fulfilled by a program like the BSCB which allows a multidisciplinary approach towards research problem solving. According to him, in the post genomic era, one cannot just restrict himself by working on a one protein-one system for his entire career. He continued, “Even if all mathematicians, physicist, chemist, biologist work together don’t know when we will have an answer about how the life came from?” Therefore it is essential to widen one’s research field by collaborating with scientists working in different research fields. “If you start with a multidisciplinary mind set up from the graduate level, that will be really great”

“I never thought about coming back to my old place but then the environment of the department, the advantage of knowing many people around, and of course the multidisciplinary nature of the program attracted me”
–Dr. Cheng, discussing his return to UTMB.

Xiaodong’s frankness and jovial nature instigated me to ask him about his early part of scientific life. His narration seemed like a wonderful journey of a budding scientist. Xiaodong’s research interests developed when he pursued his undergraduate studies. During his undergraduate days, he worked with a young enthusiastic scientist who inspired him and developed in him a keen research interest. Xiaodong then moved on to Shanghai Institute of Biochemistry to do his masters and it was during this time when he got the opportunity to work with a world renowned scientist, Wang Ying-lai who set a wonderful example as a hard working and dedicated mentor.“I remember when we celebrated his 80th birthday during my second year” Xiaodong recollects his memories of this great scientist, and adds “My mentor used to come to the lab earlier than anybody else.” Then Dr. Cheng set his feet in the US and joined UTMB as a graduate student under the guidance of Dr.James Lee after which he pursued his post doctoral research with Dr.Susan S. Taylor in Univeristy of California, San Diego. Xiaodong’s scientific life has been influenced by every scientist he worked with. Even after joining UTMB as a faculty member, he has always been inspired by Dr. James Halpert who is currently the head of the Pharmacology department. So, when I asked him on who his scientific idol was, he replied that every scientist was unique and had his or her own strengths and weaknesses and therefore he didn’t have anyone to mention in specific and considers every scientist with whom he worked with made a difference to him in his scientific life. Then he smiled and continued by a deeply touching response, “I think I learnt the most from my students”

I continued the interview on asking about what his scientific goal was, for which he laughed out open heartedly and then replied that he is deeply interested in unraveling the mystery of how cancer derives, evolves and spreads out. He expresses his interest in researching on finding a cure for cancer too.

Xiaodong has already made a significant amount of contributions in his academic career. During his post doctoral research training, he discovered that phosphoinositide-dependent protein kinase 1 (PDK1) activates protein kinase A (PKA). In his own words, he said,“I find it very interesting because for long time people thought PKA is autophosphorylated in the cell and they don’t need any upstream kinase to activate them. Our study showed that PDK1 is responsible for phosphorylation and therefore activation of PKA.” Further, his own research group showed that although the Epac (exchange proteins directly activated by cAMP) and PKA are activated by the same common messenger cAMP, cAMP dynamics and the activation of its effectors are precisely controlled spatiotemporally. More recently, regarding oncogenic transformation by KRAS using the human cancer model his group got some very interesting results.

According to Xiaodong, the discovery of DNA double helix in biology and the launching of internet in whole research world were the two most important contributions in all of science. “When I was graduate student I do remember how difficult it was without the internet”, he added.

...he smiled and continued by a deeply touching response, “I think I learnt the most from my students.”– Ms. Roychowdhury & Dr. Cheng discussing mentors and teachers.

Dr. Cheng thinks that unlike any other career, science is very much a self-dependent occupation and one has to be extremely motivated. His advice is to keep an open mind and be curious and undaring to ask any question in science. In his opinion, in addition to motivation and curiosity, a good graduate student should have good communication skills. When he said that every student should persevere when it comes to science, I asked him on how he motivates his students when things don’t proceed as expected, for which he replied that he pays a listening ear, tries to be a part of it and encourages them by telling them his own personal experiences. He thinks that basically there are two important things that one learns from a Ph.D, 1) How to think about a problem, 2) and how to solve a problem. He further adds, “Ph.D is like a journey and you will realize that you know how to deal with a research problem, and if you ultimately sail through this journey with a positive attitude I would say that you made it!”