Dengke Ma, PhD

Assistant Professor
Cardiovascular Research Institute
Department of Physiology
+1 415 502-3386

Our research is focused on understanding the mechanistic (genetic and physiological) basis of cellular and organismic stress resilience. We hope to use the knowledge from such studies to engineer cells and organisms with novel resilience traits that protect against environmental stresses, biological aging and pathological mutations/microbes/toxins. 

Many organisms in nature have evolved specialized traits to respond and adapt to severe environmental stresses, including hypothermia (cold) or hypoxia (low oxygen). For example, Arctic ground squirrels can tolerate extreme low levels of oxygen in the brain and heart during hibernation. Most nematodes, including those from the Antarctica and the common model organism C. elegans, can enter "suspended animation" states upon anoxia; they can also be frozen alive and suspend life that can be revived later virtually any long after freezing, unlike many other multicellular organisms. We use both cultured neural stem cells from hibernating Arctic ground squirrels and nematodes with extremophile-like phenotypes recapitulated in the laboratory as discovery tools to understand mechanisms of cellular and physiological resilience. Genes identified from such systems via large-scale experimental screens or computational mining often encode proteins of unusual properties that define novel mechanisms underlying cytoprotection, cellular organelle dynamics and organismic homeostasis in physiology and behaviors. Some were even acquired from extremophile microbes via horizontal gene transfers and functionally co-opted to confer stress resilience. We take advantage of findings from our research and aim to use synthetic physiology approaches to engineer biological systems that may foster new means of cytoprotection, organ transplantation, reversible cryo-preservation and therapeutics to treat ischemic, neurological and age-related disorders.

Research Summary: 
Genetic analysis of extreme physiology and stem cell biology

Websites

Publications: 

LPD-3 as a megaprotein brake for aging and insulin-mTOR signaling in C. elegans.

Cell reports

Pandey T, Wang B, Wang C, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK

Suppressing mortality and curbing cellular damage by targeting VHL.

bioRxiv : the preprint server for biology

Jiang WI, Cao Y, Xue Y, Ji Y, Winer BY, Zhang M, Singhal NS, Pierce JT, Chen S, Ma DK

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

Science advances

Jiang WI, De Belly H, Wang B, Wong A, Kim M, Oh F, DeGeorge J, Huang X, Guang S, Weiner OD, Ma DK

Early-life stress triggers long-lasting organismal resilience and longevity via tetraspanin.

bioRxiv : the preprint server for biology

Jiang WI, Belly H, Wang B, Wong A, Kim M, Oh F, DeGeorge J, Huang X, Guang S, Weiner OD, Ma DK

Acquired stress resilience through bacteria-to-nematode interdomain horizontal gene transfer.

The EMBO journal

Pandey T, Kalluraya CA, Wang B, Xu T, Huang X, Guang S, Daugherty MD, Ma DK

Natural product P57 induces hypothermia through targeting pyridoxal kinase.

Nature communications

Wang R, Xiao L, Pan J, Bao G, Zhu Y, Zhu D, Wang J, Pei C, Ma Q, Fu X, Wang Z, Zhu M, Wang G, Gong L, Tong Q, Jiang M, Hu J, He M, Wang Y, Li T, Liang C, Li W, Xia C, Li Z, Ma DK, Tan M, Liu JY, Jiang W, Luo C, Yu B, Dang Y

Acquired stress resilience through bacteria-to-nematode horizontal gene transfer.

bioRxiv : the preprint server for biology

Pandey T, Kalluraya C, Wang B, Xu T, Huang X, Guang S, Daugherty MD, Ma DK

Insulin-mTOR hyperfunction drives C. elegans aging opposed by the megaprotein LPD-3.

bioRxiv : the preprint server for biology

Pandey T, Wang B, Zu J, Deng H, Shen K, do Vale GD, McDonald JG, Ma DK

Bridge-Like Lipid Transfer Proteins (BLTPs) in C. elegans: From Genetics to Structures and Functions.

Contact (Thousand Oaks (Ventura County, Calif.))

Pandey T, Zhang J, Wang B, Ma DK

A conserved megaprotein-based molecular bridge critical for lipid trafficking and cold resilience.

Nature communications

Wang C, Wang B, Pandey T, Long Y, Zhang J, Oh F, Sima J, Guo R, Liu Y, Zhang C, Mukherjee S, Bassik M, Lin W, Deng H, Vale G, McDonald JG, Shen K, Ma DK

Co-opted genes of algal origin protect C. elegans against cyanogenic toxins.

Current biology : CB

Wang B, Pandey T, Long Y, Delgado-Rodriguez SE, Daugherty MD, Ma DK

Ethacrynic acid targets GSTM1 to ameliorate obesity by promoting browning of white adipocytes.

Protein & cell

Cui Z, Liu Y, Wan W, Xu Y, Hu Y, Ding M, Dou X, Wang R, Li H, Meng Y, Li W, Jiang W, Li Z, Li Y, Tan M, Ma DK, Ding Y, Liu JO, Luo C, Yu B, Tang Q, Dang Y

The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics.

Proceedings of the National Academy of Sciences of the United States of America

Luo S, Wang X, Bai M, Jiang W, Zhang Z, Chen Y, Ma DK

Nucleolus localization of SpyCas9 affects its stability and interferes with host protein translation in mammalian cells.

Genes & Diseases

Tan R, Du W, Liu Y, Cong X, Bai M, Jiang C, Li Z, Tan M, Ma DK, Huang Q, Jiang W, Dang Y

Resilience to Injury: A New Approach to Neuroprotection?

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

Singhal NS, Sun CH, Lee EM, Ma DK

Broadly conserved roles of TMEM131 family proteins in intracellular collagen assembly and secretory cargo trafficking.

Science advances

Zhang Z, Bai M, Barbosa GO, Chen A, Wei Y, Luo S, Wang X, Wang B, Tsukui T, Li H, Sheppard D, Kornberg TB, Ma DK

Neuronal GDPGP1 and glycogen metabolism: friend or foe?

The Journal of cell biology

Singhal NS, Lee EM, Ma DK

MDT-15/MED15 permits longevity at low temperature via enhancing lipidostasis and proteostasis.

PLoS biology

Lee D, An SWA, Jung Y, Yamaoka Y, Ryu Y, Goh GYS, Beigi A, Yang JS, Jung GY, Ma DK, Ha CM, Taubert S, Lee Y, Lee SV

WDR-23 and SKN-1/Nrf2 Coordinate with the BLI-3 Dual Oxidase in Response to Iodide-Triggered Oxidative Stress.

G3 (Bethesda, Md.)

Xu Z, Hu Y, Deng Y, Chen Y, Hua H, Huang S, Nie Q, Pan Q, Ma DK, Ma L

A genetic program mediates cold-warming response and promotes stress-induced phenoptosis in C. elegans.

eLife

Jiang W, Wei Y, Long Y, Owen A, Wang B, Wu X, Luo S, Dang Y, Ma DK

Conserved roles of C. elegans and human MANFs in sulfatide binding and cytoprotection.

Nature communications

Bai M, Vozdek R, Hnízda A, Jiang C, Wang B, Kuchar L, Li T, Zhang Y, Wood C, Feng L, Dang Y, Ma DK

Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin.

Blood

Jiang W, Zhou X, Li Z, Liu K, Wang W, Tan R, Cong X, Shan J, Zhan Y, Cui Z, Jiang L, Li Q, Shen S, Bai M, Cheng Y, Li B, Tan M, Ma DK, Liu JO, Dang Y

Multiple excitatory and inhibitory neural signals converge to fine-tune Caenorhabditis elegans feeding to food availability.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Dallière N, Bhatla N, Luedtke Z, Ma DK, Woolman J, Walker RJ, Holden-Dye L, O'Connor V

Warm up and cool down!

Oncotarget

Wang T, Ma D

Acyl-CoA Dehydrogenase Drives Heat Adaptation by Sequestering Fatty Acids.

Cell

Ma DK, Li Z, Lu AY, Sun F, Chen S, Rothe M, Menzel R, Sun F, Horvitz HR

CYP-13A12 of the nematode Caenorhabditis elegans is a PUFA-epoxygenase involved in behavioural response to reoxygenation.

The Biochemical journal

Keller J, Ellieva A, Ma DK, Ju J, Nehk E, Konkel A, Falck JR, Schunck WH, Menzel R

Cytochrome P450 drives a HIF-regulated behavioral response to reoxygenation by C. elegans.

Science (New York, N.Y.)

Ma DK, Rothe M, Zheng S, Bhatla N, Pender CL, Menzel R, Horvitz HR

Neuronal activity modifies the DNA methylation landscape in the adult brain.

Nature neuroscience

Guo JU, Ma DK, Mo H, Ball MP, Jang MH, Bonaguidi MA, Balazer JA, Eaves HL, Xie B, Ford E, Zhang K, Ming GL, Gao Y, Song H

Epigenetic choreographers of neurogenesis in the adult mammalian brain.

Nature neuroscience

Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H

Activity-dependent extrinsic regulation of adult olfactory bulb and hippocampal neurogenesis.

Annals of the New York Academy of Sciences

Ma DK, Kim WR, Ming GL, Song H

Adult neural stem cells in the mammalian central nervous system.

Cell research

Ma DK, Bonaguidi MA, Ming GL, Song H

DNA excision repair proteins and Gadd45 as molecular players for active DNA demethylation.

Cell cycle (Georgetown, Tex.)

Ma DK, Guo JU, Ming GL, Song H

Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis.

Science (New York, N.Y.)

Ma DK, Jang MH, Guo JU, Kitabatake Y, Chang ML, Pow-Anpongkul N, Flavell RA, Lu B, Ming GL, Song H

G9a and Jhdm2a regulate embryonic stem cell fusion-induced reprogramming of adult neural stem cells.

Stem cells (Dayton, Ohio)

Ma DK, Chiang CH, Ponnusamy K, Ming GL, Song H

Cellular niches for endogenous neural stem cells in the adult brain.

CNS & neurological disorders drug targets

Jordan JD, Ma DK, Ming GL, Song H

Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain.

Cell

Duan X, Chang JH, Ge S, Faulkner RL, Kim JY, Kitabatake Y, Liu XB, Yang CH, Jordan JD, Ma DK, Liu CY, Ganesan S, Cheng HJ, Ming GL, Lu B, Song H

Adult neural stem cells and repair of the adult central nervous system.

Journal of hematotherapy & stem cell research

Goh EL, Ma D, Ming GL, Song H