Dengke Ma, PhD

Associate Professor

Cardiovascular Research Institute

Research Interests

Natural and synthetic physiology of life's resilience

[email protected]

+1 415 502-3386

Websites

https://malab.ucsf.edu/

Faculty Type

Core CVRI Faculty

Research Summary: We are fascinated by the natural and synthetic physiology of life's resilience. 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 extremely low levels of oxygen in the brain and heart during hibernation. Most nematodes, including those from 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 cultured neural stem cells from hibernating Arctic ground squirrels and nematodes with extremophile-like phenotypes recapitulated in the laboratory as discovery tools to discover novel cellular and physiological resilience mechanisms. 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 organismal 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 neuroprotection, organ transplantation, reversible cryo-preservation, and therapeutics to treat ischemic, neurological, and age-related disorders.

Publications

ER-GUARD: an evolutionarily conserved antioxidant defense system at ER membranes.

bioRxiv : the preprint server for biology

Ji Z, Pandey T, de Belly H, Wang B, Weiner OD, Tang Y, Guang S, Goddard TD, Ma DK

Non-Visual Light Sensing Enhances Behavioral Memory and Drives Gene Expression in C. elegans.

bioRxiv : the preprint server for biology

Ji Z, Wang B, Chandra R, Liu J, Yang S, Long Y, Egan M, L'Etoile N, Ma DK

Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.

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

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

P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.

Leukemia

Li Q, Liu Y, Wu J, Zhu Z, Fan J, Zhai L, Wang Z, Du G, Zhang L, Hu J, Ma DK, Liu JO, Huang H, Tan M, Dang Y, Jiang W

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

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

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, De 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

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

bioRxiv : the preprint server for biology

Pandey T, Wang B, Wang C, 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

Stress-Induced Phenoptosis: Mechanistic Insights and Evolutionary Implications.

Biochemistry. Biokhimiia

Pandey T, Ma DK

GPCR signaling regulates severe stress-induced organismic death in Caenorhabditis elegans.

Aging cell

Wang C, Long Y, Wang B, Zhang C, 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

Abstract TP251: CRISPR-engineered Mouse Neural Cells Expressing An Optimized Manf Variant Reveals Mechanisms Of MANF Neuroprotection.

Stroke

Ted D Llera, Neel S Singhal, Dengke Ma

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 C. elegans homolog of human panic-disorder risk gene TMEM132D orchestrates neuronal morphogenesis through the WAVE-regulatory complex.

Molecular brain

Wang X, Jiang W, Luo S, Yang X, Wang C, Wang B, Dang Y, Shen Y, Ma DK

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

The conserved transmembrane protein TMEM-39 coordinates with COPII to promote collagen secretion and regulate ER stress response.

PLoS genetics

Zhang Z, Luo S, Barbosa GO, Bai M, Kornberg TB, Ma DK

Cytoprotection by a naturally occurring variant of ATP5G1 in Arctic ground squirrel neural progenitor cells.

eLife

Singhal NS, Bai M, Lee EM, Luo S, Cook KR, 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

Abstract TP110: Dissecting the Optimized Cytoprotective Responses of Arctic Ground Squirrels With CRISPR.

Stroke

Evan M Lee, Neel S Singhal, Meirong Bai, Dengke K Ma

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

VHL-1 inactivation and mitochondrial antioxidants rescue C. elegans dopaminergic neurodegeneration.

Protein & cell

Chen S, Luo S, Zhang Z, Ma DK

Abstract TP136: Mitochondrial Mechanisms of Resilience Revealed by Arctic Ground Squirrel Neural Cells.

Stroke

Neel S Singhal, Meirong Bai, Shuo Luo, Dengke K Ma

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

The receptor tyrosine kinase HIR-1 coordinates HIF-independent responses to hypoxia and extracellular matrix injury.

Science signaling

Vozdek R, Long Y, Ma DK

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

The neurobiology of sensing respiratory gases for the control of animal behavior.

Frontiers in biology

Ma DK, Ringstad N

CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-modulated hypoxia-induced behavioral plasticity in C. elegans.

Neuron

Ma DK, Vozdek R, Bhatla N, Horvitz HR

Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells.

Molecular brain

Ma DK, Ponnusamy K, Song MR, Ming GL, Song H

https://profiles.ucsf.edu/dengke.ma

Address

555 & 535 Mission Bay Blvd Sou, Rm 252X
UCSF Box 3118
San Francisco, CA 94158
United States