Jialing Lin, PhD

Associate Professor


Contact Information:

Office:  BMSB 935

Phone: (405) 271-2227  ext. 61216
Fax:     (405) 271-3092

Mailing Address:
940 S. L. Young Blvd., BMSB 935
Oklahoma City, OK  73104

jialing-lin@ouhsc.edu


Education:

PhD, University of Tennessee, 1994


Research Interests:

Bcl-2 family proteins regulated cell death and its relationship to development and treatment of cancer; Biosynthesis and functional structure of membrane proteins.

Programmed cell death (apoptosis) plays an essential role in embryogenesis and adult tissue homeostasis of multicellular organisms by removing unwanted and damaged cells. Impaired regulation of apoptosis is implicated in diseases from cancer to autoimmune disorder to degenerative syndrome. In fact evading apoptosis has been identified as the first of the six critical steps toward carcinogenesis. Two kinds of signals can trigger apoptosis, the death signals received by death receptors on cell surface and the stress signals such as depletion of growth factor and genotypic damages. These apoptotic signals provoke the activation of a set of proteases and nucleases that cleave critical proteins and DNAs to dismantle the cell. Various apoptotic stimuli route through mitochondria to signal the death device. Not surprisingly the decision to launch death program relies primarily on those Bcl-2 family proteins that sooner or later use the mitochondria as their battle field.

The Bcl-2 family includes anti-apoptotic Bcl-2, pro-apoptotic Bax and pro-apoptotic BH3 proteins. These proteins share sequence homology in at least one of the four Bcl-2 homology (BH) motifs. Various stress/death signals activate BH3 proteins. This enhances the interactions of BH3 proteins with the mitochondria and other Bcl-2 family proteins. A few active BH3 proteins can directly activate Bax proteins. Active Bax proteins change conformation, insert into the mitochondrial membrane and form oligomers. The Bax oligomers permeabilize the mitochondrial membrane, releasing pro-death proteins that activate caspases and nucleases and triggering apoptosis. Bcl-2 proteins bind active Bax proteins, preventing them from oligomerization in and permeabilization of the mitochondrial membrane. Many BH3 proteins can bind the Bcl-2 proteins, preventing them from interacting and inhibiting Bax proteins. The interactions among Bcl-2 family proteins are thus complex. Which interaction(s) plays a dominant role in the decision-making process during apoptosis induction has always been a hotly debated issue since the discovery of Bcl-2 family.

My group is currently addressing the following important questions about the structure and function of Bcl-2 family proteins. How Bcl-2 protects cells, and how BH3 and Bax kill cells? How Bcl-2 inhibits Bax, and how BH3 inhibits Bcl-2? What is the structure of these proteins in healthy or dying cells? What is the structure of these proteins told us about their function during cell death? Can we use the structural information to design drugs that will alter the function of these proteins? Will these drugs be effective in kill cancer cells? We are using a combination of biochemical, biophysical, cell biological and molecular approaches to answer these questions in model systems related to various cancers. We are also interested in setting up collaborations to study Bcl-2 family proteins in other disease-related model systems.


Selected Publications:

1. Niu X, Brahmbhatt H, Mergenthaler P, Zhang Z, Sang J, Daude M, Ehlert FGR,
Diederich WE, Wong E, Zhu W, Pogmore J, Nandy JP, Satyanarayana M, Jimmidi RK,
Arya P, Leber B, Lin J, Culmsee C, Yi J, Andrews DW. A Small-Molecule Inhibitor
of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes
Neuroprotection. Cell chemical biology. 2017; 24(4):493-506.e5. PubMed [journal] 
PMID: 28392146

2. Liao C, Zhang Z, Kale J, Andrews DW, Lin J, Li J. Conformational Heterogeneity of
Bax Helix 9 Dimer for Apoptotic Pore Formation. Scientific reports. 2016;
6:29502. PubMed [journal] PMID: 27381287, PMCID: PMC4933972

3. Zhang Z, Subramaniam S, Kale J, Liao C, Huang B, Brahmbhatt H, Condon SG, Lapolla
SM, Hays FA, Ding J, He F, Zhang XC, Li J, Senes A, Andrews DW, Lin J.
BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore
assembly in membranes. The EMBO journal. 2016; 35(2):208-36. PubMed [journal]
PMID: 26702098, PMCID: PMC4718459

4. Ding J, Mooers BH, Zhang Z, Kale J, Falcone D, McNichol J, Huang B, Zhang XC,
Xing C, Andrews DW, Lin J. After embedding in membranes antiapoptotic Bcl-XL
protein binds both Bcl-2 homology region 3 and helix 1 of proapoptotic Bax
protein to inhibit apoptotic mitochondrial permeabilization. The Journal of
biological chemistry. 2014; 289(17):11873-96. PubMed [journal] PMID: 24616095,
PMCID: PMC4002096

5. Medina AP, Lin J, Weigel PH. Hyaluronan synthase mediates dye translocation
across liposomal membranes. BMC biochemistry. 2012; 13:2. PubMed [journal] PMID: 
22276637, PMCID: PMC3331846

6. Zhao L, He F, Liu H, Zhu Y, Tian W, Gao P, He H, Yue W, Lei X, Ni B, Wang X, Jin 
H, Hao X, Lin J, Chen Q. Natural diterpenoid compound elevates expression of Bim 
protein, which interacts with antiapoptotic protein Bcl-2, converting it to
proapoptotic Bax-like molecule. The Journal of biological chemistry. 2012;
287(2):1054-65. PubMed [journal] PMID: 22065578, PMCID: PMC3256916

7. Ko JK, Choi KH, Peng J, He F, Zhang Z, Weisleder N, Lin J, Ma J. Amphipathic
tail-anchoring peptide and Bcl-2 homology domain-3 (BH3) peptides from Bcl-2
family proteins induce apoptosis through different mechanisms. The Journal of
biological chemistry. 2011; 286(11):9038-48. PubMed [journal] PMID: 21189256,
PMCID: PMC3059050

8. Leber B, Lin J, Andrews DW. Still embedded together binding to membranes
regulates Bcl-2 protein interactions. Oncogene. 2010; 29(38):5221-30. PubMed
[journal] PMID: 20639903

9. Ding J, Zhang Z, Roberts GJ, Falcone M, Miao Y, Shao Y, Zhang XC, Andrews DW, Lin
J. Bcl-2 and Bax interact via the BH1-3 groove-BH3 motif interface and a novel
interface involving the BH4 motif. The Journal of biological chemistry. 2010;
285(37):28749-63. PubMed [journal] PMID: 20584903, PMCID: PMC2937903

10. Zhang Z, Zhu W, Lapolla SM, Miao Y, Shao Y, Falcone M, Boreham D, McFarlane N,
Ding J, Johnson AE, Zhang XC, Andrews DW, Lin J. Bax forms an oligomer via
separate, yet interdependent, surfaces. The Journal of biological chemistry.
2010; 285(23):17614-27. PubMed [journal] PMID: 20382739, PMCID: PMC2878526

Link to full publication list >