Daohong Zhou

Daohong Zhou, M.D.

Professor And The Henry E. Innes Professorship Of Cancer Research

Department: Pharmacodynamics
Business Phone: (352) 294-8952
Business Email: zhoudaohong@cop.ufl.edu

About Daohong Zhou

Dr. Daohong Zhou is a Professor in the Department of Pharmacodynamics at the College of Pharmacy and a Professor in the Department of Radiation Oncology at the College of Medicine, University of Florida (UF) at Gainesville. He serves as the Associate Director for Translation and Drug Development and the Henry E. Innes Professorsip of Cancer Research at the UF Health Cancer Center. Dr. Zhou received his medical (1978-1983) and graduate (1983-1986) training from Yunyany Medical College of Tongji Medical University and Henan Medical University, respectively; and his postdoctoral training (1990-1992) at the Johns Hopkins University School of Medicine. Before he joined UF in 2018, he was a Professor of Pharmaceutical Sciences and the Deputy Director of the Division of Radiation Health at the College of Pharmacy and the Associate Director for Basic Research at the Winthrop P. Rockefeller Cancer Institute in the University of Arkansas for Medical Sciences (UAMS).

Dr. Daohong Zhou has published more than 100 peer reviewed scientific articles and book chapters. His research has been well supported by grants from various private and government funding agencies, including the National Cancer Institute (NCI) and National Institute of Allergy and Infectious Disease (NIAID). Dr. Daohong Zhou serves on several national and international peer review panels and as a reviewer for various scientific publications. He was a regular member of the Radiation Therapeutics and Biology Study Section at the National Institutes of Health (NIH). He is a Councilor of the Radiation Research Society (http://www.radres.org) and a co-founder of Unity Biotechnology (http://unitybiotechnology.com), a biotech that develops senolytic drugs for aging and age-related diseases.

Accomplishments

Henry E. Innes Professorsip of Cancer Research
2018-Current · University of Florida
Established Investigator of Year Award
2016 · The Arkansas Biosciences Institute
Arkansas Research Alliance Scholar
2010-2018 · Arkansas Research Alliance
The Winthrop Rockefeller Endowed Chair for Leukemia and Lymphoma Research
2010-2018 · University of Arkansas for Medical Sciences

Research Profile

Dr. Zhou’s research has been focused on investigation of the role of senescent cells in IR- and chemotherapy-induced normal tissue injury, including tissue fibrosis and long-term bone marrow suppression and leukemogenesis. His studies has led to the discovery of a number of senolytics, including ABT263-a specific Bcl-2/xl inhibitor, that can selectively kill senescent cells to rejuvenate both prematurely senescent tissue stem cells induced by IR and senescent tissue stem cells in normally aged mice. This discovery may lead to new therapeutics for various age-related diseases and the side effects induced by chemotherapy and IR. More recently, he developed several proteolysis targeting chimeras (PROTACs) that can target Bcl-xl and other proteins of interest for degradation via the ubiquitination and proteasome system. He found that Bcl-xl PROTACs can selectively induce Bcl-xl degradation in senescent cells and various cancer cells but not in platelets, suggesting that Bcl-xl PROTACs have the potential to be developed as a better senolytic and anticancer agent than ABT263 by not causing thrombocytopenia. Using the PROTAC drug development platform, he is developing additional specific antitumor agents.

Publications

2021
CD177 modulates the function and homeostasis of tumor-infiltrating regulatory T cells.
Nature communications. 12(1) [DOI] 10.1038/s41467-021-26091-4. [PMID] 34599187.
2021
Cellular senescence in lymphoid organs and immunosenescence.
Aging. 13(15):19920-19941 [DOI] 10.18632/aging.203405. [PMID] 34382946.
2021
Dietary Methionine Deficiency Enhances Genetic Instability in Murine Immune Cells.
International journal of molecular sciences. 22(5) [DOI] 10.3390/ijms22052378. [PMID] 33673497.
2021
Discovery of a Novel BCL-XL PROTAC Degrader with Enhanced BCL-2 Inhibition.
Journal of medicinal chemistry. 64(19):14230-14246 [DOI] 10.1021/acs.jmedchem.1c00517. [PMID] 34533954.
2021
Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-XL Specific Degrader DT2216.
Molecular cancer therapeutics. [DOI] 10.1158/1535-7163.MCT-21-0474. [PMID] 34667112.
2021
Proteolysis-targeting chimera against BCL-XL destroys tumor-infiltrating regulatory T cells.
Nature communications. 12(1) [DOI] 10.1038/s41467-021-21573-x. [PMID] 33627663.
2021
PUMA facilitates EMI1-promoted cytoplasmic Rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells.
Signal transduction and targeted therapy. 6(1) [DOI] 10.1038/s41392-021-00510-w. [PMID] 33785736.
2021
Senescence-associated hyper-activation to inflammatory stimuli in vitro.
Aging. 13(15):19088-19107 [DOI] 10.18632/aging.203396. [PMID] 34375950.
2021
The Curcumin Analog EF24 is Highly Active Against Chemotherapy- Resistant Melanoma Cells.
Current cancer drug targets. 21(7):608-618 [DOI] 10.2174/1568009621666210303092921. [PMID] 33655859.
2021
Therapy-Induced Senescence: Opportunities to Improve Anticancer Therapy.
Journal of the National Cancer Institute. 113(10):1285-1298 [DOI] 10.1093/jnci/djab064. [PMID] 33792717.
2020
Assays and technologies for developing proteolysis targeting chimera degraders.
Future medicinal chemistry. 12(12):1155-1179 [DOI] 10.4155/fmc-2020-0073. [PMID] 32431173.
2020
Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling.
Oncogene. 39(14):2877-2889 [DOI] 10.1038/s41388-020-1203-x. [PMID] 32042113.
2020
Depletion of senescent-like neuronal cells alleviates cisplatin-induced peripheral neuropathy in mice.
Scientific reports. 10(1) [DOI] 10.1038/s41598-020-71042-6. [PMID] 32843706.
2020
Deuteration of the farnesyl terminal methyl groups of δ-tocotrienol and its effects on the metabolic stability and ability of inducing G-CSF production.
Bioorganic & medicinal chemistry. 28(11) [DOI] 10.1016/j.bmc.2020.115498. [PMID] 32291146.
2020
Discovery of IAP-recruiting BCL-XL PROTACs as potent degraders across multiple cancer cell lines.
European journal of medicinal chemistry. 199 [DOI] 10.1016/j.ejmech.2020.112397. [PMID] 32388279.
2020
Discovery of PROTAC BCL-XL degraders as potent anticancer agents with low on-target platelet toxicity.
European journal of medicinal chemistry. 192 [DOI] 10.1016/j.ejmech.2020.112186. [PMID] 32145645.
2020
DT2216-a Bcl-xL-specific degrader is highly active against Bcl-xL-dependent T cell lymphomas.
Journal of hematology & oncology. 13(1) [DOI] 10.1186/s13045-020-00928-9. [PMID] 32677976.
2020
FoxM1 insufficiency hyperactivates Ect2–RhoA–mDia1 signaling to drive cancer.
Nature Cancer. 12(1):1010-1024
2020
IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis.
The Journal of clinical investigation. 130(10):5493-5507 [DOI] 10.1172/JCI134091. [PMID] 32955487.
2020
Increased marrow adipogenesis does not contribute to age-dependent appendicular bone loss in female mice.
Aging cell. 19(11) [DOI] 10.1111/acel.13247. [PMID] 33048436.
2020
Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity.
Aging cell. 19(3) [DOI] 10.1111/acel.13117. [PMID] 32064756.
2020
Latexin regulation by HMGB2 is required for hematopoietic stem cell maintenance.
Haematologica. 105(3):573-584 [DOI] 10.3324/haematol.2018.207092. [PMID] 31171637.
2020
Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence.
JCI insight. 5(19) [DOI] 10.1172/jci.insight.138815. [PMID] 32870816.
2020
PROTACs are effective in addressing the platelet toxicity associated with BCL-XL inhibitors.
Exploration of targeted anti-tumor therapy. 1:259-272 [DOI] 10.37349/etat.2020.00017. [PMID] 34296214.
2020
Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies.
Journal of hematology & oncology. 13(1) [DOI] 10.1186/s13045-020-00924-z. [PMID] 32718354.
2020
PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics.
Oncogene. 39(26):4909-4924 [DOI] 10.1038/s41388-020-1336-y. [PMID] 32475992.
2020
Sustained fetal hematopoiesis causes juvenile death from leukemia: evidence from a dual-age-specific mouse model.
Blood advances. 4(15):3728-3740 [DOI] 10.1182/bloodadvances.2020002326. [PMID] 32777070.
2020
Synthesis and Liver Microsomal Metabolic Stability Studies of a Fluorine-Substituted δ-Tocotrienol Derivative.
ChemMedChem. 15(6):506-516 [DOI] 10.1002/cmdc.201900676. [PMID] 31957223.
2020
Targeting anti-apoptotic BCL-2 family proteins for cancer treatment.
Future medicinal chemistry. 12(7):563-565 [DOI] 10.4155/fmc-2020-0004. [PMID] 32083493.
2020
Using proteolysis-targeting chimera technology to reduce navitoclax platelet toxicity and improve its senolytic activity.
Nature communications. 11(1) [DOI] 10.1038/s41467-020-15838-0. [PMID] 32332723.
2019
A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity.
Nature medicine. 25(12):1938-1947 [DOI] 10.1038/s41591-019-0668-z. [PMID] 31792461.
2019
Cellular senescence and radiation-induced pulmonary fibrosis.
Translational research : the journal of laboratory and clinical medicine. 209:14-21 [DOI] 10.1016/j.trsl.2019.03.006. [PMID] 30981698.
2019
Cellular Senescence: Defining a Path Forward.
Cell. 179(4):813-827 [DOI] 10.1016/j.cell.2019.10.005. [PMID] 31675495.
2019
Elimination of senescent osteoclast progenitors has no effect on the age-associated loss of bone mass in mice.
Aging cell. 18(3) [DOI] 10.1111/acel.12923. [PMID] 30773784.
2019
Hectd3 promotes pathogenic Th17 lineage through Stat3 activation and Malt1 signaling in neuroinflammation.
Nature communications. 10(1) [DOI] 10.1038/s41467-019-08605-3. [PMID] 30741923.
2019
Identification of novel breakpoints for locus- and region-specific translocations in 293 cells by molecular cytogenetics before and after irradiation
Scientific Reports. 9(1) [DOI] 10.1038/s41598-019-47002-0. [PMID] 31332273.
2019
Systemic clearance of p16 INK4a ‐positive senescent cells mitigates age‐associated intervertebral disc degeneration
Aging Cell. 18(3) [DOI] 10.1111/acel.12927. [PMID] 30900385.
2019
The curcumin analog EF24 is a novel senolytic agent.
Aging. 11(2):771-782 [DOI] 10.18632/aging.101787. [PMID] 30694217.
2019
Utilizing PROTAC technology to address the on-target platelet toxicity associated with inhibition of BCL-XL.
Chemical communications (Cambridge, England). 55(98):14765-14768 [DOI] 10.1039/c9cc07217a. [PMID] 31754664.
2018
Cellular Senescence, Geroscience, Cancer and Beyond
Aging-US. 10(9):2233-2237 [DOI] 10.18632/aging.101546. [PMID] 30194819.
2018
Host genetic susceptibility to Clostridium difficile infections in patients undergoing autologous stem cell transplantation: a genome-wide association study
Supportive Care in Cancer. 26(9):3127-3134 [DOI] 10.1007/s00520-018-4173-6.
2018
M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion.
Blood advances. 2(8):859-870 [DOI] 10.1182/bloodadvances.2018015685. [PMID] 29666049.
2018
NOS2 deficiency has no influence on the radiosensitivity of the hematopoietic system.
Cell & bioscience. 8 [DOI] 10.1186/s13578-018-0228-0. [PMID] 29736233.
2018
Oxidation resistance 1 is a novel senolytic target.
Aging cell. 17(4) [DOI] 10.1111/acel.12780. [PMID] 29766639.
2018
Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation.
Bioorganic & medicinal chemistry. 26(14):3925-3938 [DOI] 10.1016/j.bmc.2018.06.013. [PMID] 29925484.
2018
Senolytic activity of piperlongumine analogues: Synthesis and biological evaluation.
Bioorg Med Chem. 26(14):3925-3938
2018
The Wave2 scaffold Hem-1 is required for transition of fetal liver hematopoiesis to bone marrow.
Nature communications. 9(1) [DOI] 10.1038/s41467-018-04716-5. [PMID] 29915352.
2017
28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis.
Life sciences in space research. 13:39-44 [DOI] 10.1016/j.lssr.2017.03.003. [PMID] 28554508.
2017
28Si total body irradiation injures bone marrow hematopoietic stem cells via induction of cellular apoptosis.
Life Sci Space Res (Amst).. (13):39-44
2017
An oral HemokineTM, α-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo
Blood Cells, Molecules, and Diseases. 63:1-8 [DOI] 10.1016/j.bcmd.2016.10.021. [PMID] 27888688.
2017
Autophagy Promotes the Repair of Radiation-Induced DNA Damage in Bone Marrow Hematopoietic Cells via Enhanced STAT3 Signaling.
Radiation research. 187(3):382-396 [DOI] 10.1667/RR14640.1. [PMID] 28327001.
2017
Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse.
Cancer discovery. 7(2):165-176 [DOI] 10.1158/2159-8290.CD-16-0241. [PMID] 27979832.
2017
DNA damage and senescence in osteoprogenitors expressing Osx1 may cause their decrease with age.
Aging cell. 16(4):693-703 [DOI] 10.1111/acel.12597. [PMID] 28401730.
2017
Early assessment of dosimetric and biological differences of total marrow irradiation versus total body irradiation in rodents.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 124(3):468-474 [DOI] 10.1016/j.radonc.2017.07.018. [PMID] 28778346.
2017
Evasion of regulatory phosphorylation by an alternatively spliced isoform of Musashi2.
Scientific reports. 7(1) [DOI] 10.1038/s41598-017-11917-3. [PMID] 28912529.
2017
Inhibition of Bcl-2/xl With ABT-263 Selectively Kills Senescent Type II Pneumocytes and Reverses Persistent Pulmonary Fibrosis Induced by Ionizing Radiation in Mice.
International journal of radiation oncology, biology, physics. 99(2):353-361 [DOI] 10.1016/j.ijrobp.2017.02.216. [PMID] 28479002.
2017
Inter-Strain Differences in LINE-1 DNA Methylation in the Mouse Hematopoietic System in Response to Exposure to Ionizing Radiation.
International journal of molecular sciences. 18(7) [DOI] 10.3390/ijms18071430. [PMID] 28677663.
2017
Latexin Inactivation Enhances Survival and Long-Term Engraftment of Hematopoietic Stem Cells and Expands the Entire Hematopoietic System in Mice
Stem Cell Reports. 8(4):991-1004 [DOI] 10.1016/j.stemcr.2017.02.009. [PMID] 28330618.
2017
Low doses of oxygen ion irradiation cause long-term damage to bone marrow hematopoietic progenitor and stem cells in mice.
PloS one. 12(12) [DOI] 10.1371/journal.pone.0189466. [PMID] 29232383.
2017
Nuclear localization of Beclin 1 promotes radiation-induced DNA damage repair independent of autophagy.
Scientific reports. 7 [DOI] 10.1038/srep45385. [PMID] 28345663.
2017
Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice.
International journal of radiation biology. 93(12):1312-1320 [DOI] 10.1080/09553002.2017.1356941. [PMID] 28782442.
2016
Biomedical Applications of Gut Stem Cells: Gaining First-Hand Insights for Developing Therapy for the Future
Journal of Stem Cell Research & Therapeutics. 1(3) [DOI] 10.15406/jsrt.2016.01.00023.
2016
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.
Nature medicine. 22(1):78-83 [DOI] 10.1038/nm.4010. [PMID] 26657143.
2016
Discovery of piperlongumine as a potential novel lead for the development of senolytic agents.
Aging. 8(11):2915-2926 [DOI] 10.18632/aging.101100. [PMID] 27913811.
2016
Hematopoietic Stem Cells from Ts65Dn Mice Are Deficient in the Repair of DNA Double-Strand Breaks.
Radiation research. 185(6):630-7 [DOI] 10.1667/RR14407.1. [PMID] 27243896.
2016
Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases.
Radiation research. 186(2):153-61 [DOI] 10.1667/RR14445.1. [PMID] 27387862.
2016
Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.
PloS one. 11(7) [DOI] 10.1371/journal.pone.0158097. [PMID] 27367604.
2016
Marrow damage and hematopoietic recovery following allogeneic bone marrow transplantation for acute leukemias: Effect of radiation dose and conditioning regimen
Radiotherapy and Oncology. 118(1):65-71 [DOI] 10.1016/j.radonc.2015.11.012. [PMID] 26653357.
2016
Synthesis of (2R,8′ S,3′ E)-δ-tocodienol, a tocoflexol family member designed to have a superior pharmacokinetic profile compared to δ-tocotrienol.
Tetrahedron. 72(27-28):4001-4006 [PMID] 27773949.
View on: PubMed
2016
The Vitamin E Analog Gamma-Tocotrienol (GT3) and Statins Synergistically Up-Regulate Endothelial Thrombomodulin (TM).
International journal of molecular sciences. 17(11) [PMID] 27869747.
View on: PubMed
2016
Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy.
Blood. 127(15):1912-22 [DOI] 10.1182/blood-2015-05-646216. [PMID] 26764354.
2015
EEPD1 Rescues Stressed Replication Forks and Maintains Genome Stability by Promoting End Resection and Homologous Recombination Repair.
PLoS genetics. 11(12) [DOI] 10.1371/journal.pgen.1005675. [PMID] 26684013.
2015
Gene expression profiling in non-human primate jejunum, ileum and colon after total-body irradiation: a comparative study of segment-specific molecular and cellular responses.
BMC genomics. 16 [DOI] 10.1186/s12864-015-2168-y. [PMID] 26589571.
2015
Granulocyte colony-stimulating factor exacerbates hematopoietic stem cell injury after irradiation
Cell & Bioscience. 5(1) [DOI] 10.1186/s13578-015-0057-3. [PMID] 26609358.
2015
GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis.
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 23(3):841-9 [DOI] 10.1007/s00520-014-2406-x. [PMID] 25218607.
2015
Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice.
Free Radic Biol Med.. 16(87):15-25
2015
Thrombomodulin contributes to gamma tocotrienol-mediated lethality protection and hematopoietic cell recovery in irradiated mice.
PloS one. 10(4) [DOI] 10.1371/journal.pone.0122511. [PMID] 25860286.
2015
Total Body Irradiation in the “Hematopoietic” Dose Range Induces Substantial Intestinal Injury in Non-Human Primates.
Radiation research. 184(5):545-53 [DOI] 10.1667/RR14191.1. [PMID] 26495870.
2015
Whole-body proton irradiation causes long-term damage to hematopoietic stem cells in mice.
Radiation research. 183(2):240-8 [DOI] 10.1667/RR13887.1. [PMID] 25635345.
2014
Bone marrow transplantation helps restore the intestinal mucosal barrier after total body irradiation in mice.
Radiation research. 181(3):229-39 [DOI] 10.1667/RR13548.1. [PMID] 24568131.
2014
C/EBPδ deficiency sensitizes mice to ionizing radiation-induced hematopoietic and intestinal injury.
PloS one. 9(4) [DOI] 10.1371/journal.pone.0094967. [PMID] 24747529.
2014
Exonuclease 1 is essential for maintaining genomic stability and the proliferative capacity of neural but not hematopoietic stem cells.
Stem cell research. 12(1):250-9 [DOI] 10.1016/j.scr.2013.11.001. [PMID] 24280419.
2014
Exposure to low-dose (56)Fe-ion radiation induces long-term epigenetic alterations in mouse bone marrow hematopoietic progenitor and stem cells.
Radiation research. 182(1):92-101 [DOI] 10.1667/RR13580.1. [PMID] 24960414.
2014
Genome-wide scan identifies variant in 2q12.3 associated with risk for multiple myeloma.
Blood. 124(12):2001-3 [DOI] 10.1182/blood-2014-07-586701. [PMID] 25237182.
2014
Hematopoietic stem cell injury induced by ionizing radiation.
Antioxidants & redox signaling. 20(9):1447-62 [DOI] 10.1089/ars.2013.5635. [PMID] 24124731.
2014
IKKβ regulates endothelial thrombomodulin in a Klf2-dependent manner
Journal of Thrombosis and Haemostasis. 12(9):1533-1544 [DOI] 10.1111/jth.12664. [PMID] 25039491.
2014
Latexin sensitizes leukemogenic cells to gamma-irradiation-induced cell-cycle arrest and cell death through Rps3 pathway
Cell Death & Disease. 5(10):e1493-e1493 [DOI] 10.1038/cddis.2014.443. [PMID] 25341047.
2014
Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence.
Transplantation. 97(1):20-9 [DOI] 10.1097/TP.0b013e3182a7fcf8. [PMID] 24092377.
2014
Reactive oxygen species in normal and tumor stem cells.
Advances in cancer research. 122:1-67 [DOI] 10.1016/B978-0-12-420117-0.00001-3. [PMID] 24974178.
2014
Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner.
Blood. 123(20):3105-15 [DOI] 10.1182/blood-2013-07-515619. [PMID] 24622326.
2013
BMS-345541 sensitizes MCF-7 breast cancer cells to ionizing radiation by selective inhibition of homologous recombinational repair of DNA double-strand breaks.
Radiation research. 179(2):160-70 [DOI] 10.1667/RR3034.1. [PMID] 23259762.
2013
CD34+ cells from patients with myelodysplastic syndrome present different p21 dependent premature senescence
Leukemia Research. 37(3):333-340 [DOI] 10.1016/j.leukres.2012.11.006.
2013
Hematopoietic stem cell senescence and cancer therapy-induced long-term bone marrow injury.
Translational cancer research. 2(5):397-411 [PMID] 24605290.
View on: PubMed
2013
PARP1 is required for chromosomal translocations.
Blood. 121(21):4359-65 [DOI] 10.1182/blood-2012-10-460527. [PMID] 23568489.
2013
Resveratrol ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice.
Free radical biology & medicine. 54:40-50 [DOI] 10.1016/j.freeradbiomed.2012.10.530. [PMID] 23124026.
2013
Sphingomyelin synthase 1 activity is regulated by the BCR-ABL oncogene.
J Lipid Res.. (54):794-805
2013
The effects of p38 MAPK inhibition combined with G-CSF administration on the hematoimmune system in mice with irradiation injury.
PloS one. 8(4) [DOI] 10.1371/journal.pone.0062921. [PMID] 23646161.
2012
A sensitive and quantitative polymerase chain reaction-based cell free in vitro non-homologous end joining assay for hematopoietic stem cells.
PloS one. 7(3) [DOI] 10.1371/journal.pone.0033499. [PMID] 22448248.
2012
Inhibition of p38 MAPK activity promotes ex vivo expansion of human cord blood hematopoietic stem cells
Annals of Hematology. 91(6):813-823 [DOI] 10.1007/s00277-011-1397-7.
2012
Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity.
Nature medicine. 18(7):1123-9 [DOI] 10.1038/nm.2813. [PMID] 22729286.
2012
Sensitization of tumor cells to cancer therapy by molecularly targeted inhibition of the inhibitor of nuclear factor κB kinase.
Translational cancer research. 1(2):100-108 [PMID] 22953243.
View on: PubMed
2012
Sphingomyelin synthase 1 activity is regulated by theBCR-ABLoncogene
Journal of Lipid Research. 54(3):794-805 [DOI] 10.1194/jlr.m033985.
2012
The glutathione disulfide mimetic NOV-002 inhibits cyclophosphamide-induced hematopoietic and immune suppression by reducing oxidative stress.
Free radical biology & medicine. 52(9):1560-8 [DOI] 10.1016/j.freeradbiomed.2012.02.007. [PMID] 22343421.
2011
Autophagy regulates ROS-induced cellular senescence via p21 in a p38 MAPKα dependent manner
Experimental Gerontology. 46(11):860-867 [DOI] 10.1016/j.exger.2011.07.005.
2011
Hematopoietic stem cell senescence and bone marrow suppression and failure (Invited review and plenary presentation at the 13th Chinese Association of Experimental Hematology Meeting).
J Exp Hematol. (19):S6-14
2011
IKKβ regulates the repair of DNA double-strand breaks induced by ionizing radiation in MCF-7 breast cancer cells.
PloS one. 6(4) [DOI] 10.1371/journal.pone.0018447. [PMID] 21490922.
2011
Inhibition of p38 MAPK attenuates ionizing radiation-induced hematopoietic cell senescence and residual bone marrow injury.
Radiation research. 176(6):743-52 [PMID] 22014293.
View on: PubMed
2011
Inhibition of p38 mitogen-activated protein kinase promotes ex vivo hematopoietic stem cell expansion.
Stem cells and development. 20(7):1143-52 [DOI] 10.1089/scd.2010.0413. [PMID] 21198398.
2011
MicroRNA Regulation of Ionizing Radiation-Induced Premature Senescence.
Int J Radiat Oncol Biol Phys. (81):839-848
2011
Mitigation of ionizing radiation-induced bone marrow suppression by p38 inhibition and G-CSF administration.
Journal of radiation research. 52(6):712-6 [PMID] 21971035.
View on: PubMed
2011
Mn(III) meso-tetrakis-(N-ethylpyridinium-2-yl) porphyrin mitigates total body irradiation-induced long-term bone marrow suppression.
Free radical biology & medicine. 51(1):30-7 [DOI] 10.1016/j.freeradbiomed.2011.04.016. [PMID] 21565268.
2011
NADPH oxidase inhibition attenuates total body irradiation-induced haematopoietic genomic instability.
Mutagenesis. 26(3):431-5 [DOI] 10.1093/mutage/ger001. [PMID] 21415439.
2011
Reactive oxygen species and hematopoietic stem cell senescence.
International journal of hematology. 94(1):24-32 [DOI] 10.1007/s12185-011-0872-1. [PMID] 21567162.
2011
Reduction of radiation-induced vascular nitrosative stress by the vitamin E analog γ-tocotrienol: evidence of a role for tetrahydrobiopterin.
International journal of radiation oncology, biology, physics. 79(3):884-91 [DOI] 10.1016/j.ijrobp.2010.08.032. [PMID] 20950957.
2010
Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition
Journal of Clinical Investigation. 120(7):2528-2536 [DOI] 10.1172/jci41402.
2010
Total body irradiation causes residual bone marrow injury by induction of persistent oxidative stress in murine hematopoietic stem cells.
Free radical biology & medicine. 48(2):348-56 [DOI] 10.1016/j.freeradbiomed.2009.11.005. [PMID] 19925862.
2010
Unmyelinated auditory type I spiral ganglion neurons in congenic Ly5.1 mice
The Journal of Comparative Neurology. 518(16):3254-3271 [DOI] 10.1002/cne.22398.
2008
Dependence on PI3K/Akt signaling for malignant rhabdoid tumor cell survival
Cancer Chemotherapy and Pharmacology. 63(5):783-791 [DOI] 10.1007/s00280-008-0796-5.
2007
Busulfan-induced senescence is dependent on ROS production upstream of the MAPK pathway
Free Radical Biology and Medicine. 42(12):1858-1865 [DOI] 10.1016/j.freeradbiomed.2007.03.020.
2006
Busulfan selectively induces cellular senescence but not apoptosis in WI38 fibroblasts via a p53-independent but extracellular signal-regulated kinase-p38 mitogen-activated protein kinase-dependent mechanism.
The Journal of pharmacology and experimental therapeutics. 319(2):551-60 [PMID] 16882877.
View on: PubMed
2006
Busulfan Selectively Induces Cellular Senescence Via a p53-Independent but Erk-p38 MAPK-Dependent Mechanism.
Blood. 108(11):3199-3199 [DOI] 10.1182/blood.v108.11.3199.3199.
2006
Cancer Therapy-Induced Residual Bone Marrow Injury: Mechanisms of Induction and Implication for Therapy
Current Cancer Therapy Reviews. 2(3):271-279 [DOI] 10.2174/157339406777934717.
2006
Contribution of bone marrow hematopoietic stem cells to adult mouse inner ear: Mesenchymal cells and fibrocytes
The Journal of Comparative Neurology. 496(2):187-201 [DOI] 10.1002/cne.20929.
2006
Hematopoietic Stem Cell Senescence and Long-Term Bone Marrow Injury.
Cell Cycle. (5):35-38
2006
Nuclear Factor  B Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss
Journal of Neuroscience. 26(13):3541-3550 [DOI] 10.1523/jneurosci.2488-05.2006.
2006
Total body irradiation selectively induces murine hematopoietic stem cell senescence.
Blood. 107(1):358-66 [PMID] 16150936.
View on: PubMed
2005
Radioprotectors: current status and new directions.
Radiat Res.. (163):704-705
2005
Sphingosine kinase 1 is up‐regulated in colon carcinogenesis
The FASEB Journal. 20(2):386-388 [DOI] 10.1096/fj.05-4331fje.
2004
Activation of nuclear factor kappaB In vivo selectively protects the murine small intestine against ionizing radiation-induced damage.
Cancer research. 64(17):6240-6 [PMID] 15342410.
View on: PubMed
2004
Inhibition of phosphatidylinostol 3-kinase uncouples H2O2-induced senescent phenotype and cell cycle arrest in normal human diploid fibroblasts.
Experimental cell research. 298(1):188-96 [PMID] 15242773.
View on: PubMed
2004
Lack of the NF-kB p50 or p65 gene sensitizes mice to ionizing radiation by increasing intestinal epithelial damage.
Cancer Research. (64):6240-6246
2004
Prodrug Modification Increases Potassium Tricyclo[5.2.1.02,6]-decan-8-yl Dithiocarbonate (D609) Chemical Stability and Cytotoxicity against U937 Leukemia Cells
Journal of Pharmacology and Experimental Therapeutics. 309(3):1051-1059 [DOI] 10.1124/jpet.103.064600.
2004
Role of Phosphatidylinositol-3-Kinase in Oxidative Stress-Induced Premature Senescence in Human Diploid Fibroblasts.
Experimental Cell Research. (289):188-196
2004
Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937 human monocytic leukemia cells
Experimental Cell Research. 292(2):385-392 [DOI] 10.1016/j.yexcr.2003.10.001.
2003
Cellular origin of ionizing radiation‐induced NF‐κB activationin vivoand role of NF‐κB in ionizing radiation‐induced lymphocyte apoptosis
International Journal of Radiation Biology. 79(11):849-861 [DOI] 10.1080/09553000310001622814.
2003
Derivatives of Xanthic Acid are Novel Antioxidants: Application to Synaptosomes
Free Radical Research. 37(4):355-365 [DOI] 10.1080/1071576021000040664.
2003
Expression of TNFα by CD3+ and F4/80+ cells following irradiation preconditioning and allogeneic spleen cell transplantation
Bone Marrow Transplantation. 33(4):359-365 [DOI] 10.1038/sj.bmt.1704362.
2003
Ionizing radiation and busulfan induce premature senescence in murine bone marrow hematopoietic cells.
Cancer research. 63(17):5414-9 [PMID] 14500376.
View on: PubMed
2003
Ionizing radiation and busulfan inhibit murine bone marrow cell hematopoietic function via apoptosis-dependent and -independent mechanisms.
Experimental hematology. 31(12):1348-56 [PMID] 14662344.
View on: PubMed
2002
Phosphatidylinositol-3-Kinase–Akt Kinase and p42/p44 Mitogen-Activated Protein Kinases Mediate Neurotrophic and Excitoprotective Actions of a Secreted Form of Amyloid Precursor Protein
Experimental Neurology. 175(2):407-414 [DOI] 10.1006/exnr.2002.7920.
2001
A comparative study on cockroach allergen and ovalbumin induced allergic sensitization and asthmatic responses in Hartley guinea pigs.
Respiratory Physiology. (125):239-247
2001
D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant.
J. Pharmacol. Exp. Ther.. (298):103-109
2001
Effects of NF-κB1 (p50) targeted gene disruption on ionizing radiation-induced NF-κB activation and TNFα, IL-1α, IL-1β and IL-6 mRNA expression in vivo
International Journal of Radiation Biology. 77(7):763-772 [DOI] 10.1080/09553000110050047.
2000
Airway hyperresponsiveness to cigarette smoke in ovalbumin-sensitized guinea pigs.
Am. J. Respir. Cri. Care Med.. (161):73-80
2000
Neuroprotective role for the p50 subunit of NF-kB in an experimental model of Huntington’s disease.
J. Mol. Neurosci.. (15):31-44
2000
Pivotal roles for acidic sphigomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal death.
J. Mol. Neurosci.. (15):85-97
1999
Ionizing radiation induces tissue-specific activation of Nuclear Factor-B in vivo.
Radiat. Res.. (151):703-709
1999
Lack of the p50 Subunit of Nuclear Factor-κB Increases the Vulnerability of Hippocampal Neurons to Excitotoxic Injury
The Journal of Neuroscience. 19(20):8856-8865 [DOI] 10.1523/jneurosci.19-20-08856.1999.
1998
A dose-response relationship between exposure to cockroach allergens and induction of sensitization in an experimental asthma in Hartley guinea pigs
Journal of Allergy and Clinical Immunology. 101(5):653-659 [DOI] 10.1016/s0091-6749(98)70174-5.
1998
Effects of cockroach antigen (Cra) sensitization on the contractility of airway smooth muscles in asthmatic guinea pigs.
Int. Arch Allergy Immunol.. (116):132-139
1996
Synergistic Effect of IL-6 on Stressors and IL-1 Induced Activation of the Hypothalamic-Pituitary-Adrenal Axis.
Neuroendocrinology. (63):227-236
1995
A potential role for prostaglandin E2 in the central nervous system as a hormonal modulator of lymphocyte function.
Am. J. Physiol.. (269):92-97
1995
Suppression of lymphocyte mitogenesis in different rat strains exposed to footshock during early diurnal and nocturnal time periods
Psychoneuroendocrinology. 20(8):821-835 [DOI] 10.1016/0306-4530(95)00009-7.
1994
Effect of One or More Footshocks on Spleen and Blood Lymphocyte Proliferation in Rats
Brain, Behavior, and Immunity. 8(1):57-65 [DOI] 10.1006/brbi.1994.1005.
1993
Exposure to physical and psychological stressors elevates plasma interleukin 6: relationship to the activation of hypothalamic-pituitary-adrenal axis.
Endocrinology. 133(6):2523-2530 [DOI] 10.1210/endo.133.6.8243274.
1993
Increased production of TGF-beta and interleukin 6 by aged spleen cells.
Immunol. Lett. (36):7-12
1992
Age-related changes in the expression of TGF-beta receptor on CD4+ and CD8+ subsets of T cells.
Aging, Immunol and Infect. Dis.. (3):217-226
1992
Possible inhibitory effects of interleukin 6 on immunity in burn patients.
Arch. Surg. . (127):65-69
1991
Pathologic concentrations of interleukin 6 inhibit T cell responses via induction of activation of TGF‐β
The FASEB Journal. 5(11):2582-2585 [DOI] 10.1096/fasebj.5.11.1868982.

Grants

Apr 2021 ACTIVE
Proteolysis-targeting chimera against BCL-XL inhibits breast cancer metastasis
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Apr 2021 ACTIVE
Selecting a Drug Development Candidate for Cancer Treatment
Role: Co-Investigator
Funding: DIALECTIC THERAPEUTICS
Jan 2021 ACTIVE
Developing a Novel PROTAC-Based NR4A1 Degrader for Breast Cancer Therapy
Role: Co-Investigator
Funding: US ARMY MED RES ACQUISITION
Dec 2020 ACTIVE
Sanofi 2020 iAwards
Role: Co-Investigator
Funding: SANOFI
Sep 2020 ACTIVE
Identifying Novel Senolytic Agents and Molecular Targets
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Jun 2020 ACTIVE
Intercollaborative Radiation Countermeasure (INTERACT) Consortium for Advanced Development of Medical Countermeasures to Mitigate/Treat Acute and Delayed Radiation Syndromes
Role: Principal Investigator
Funding: UNIV OF MARYLAND BALTIMORE via NATL INST OF HLTH NIAID
Jun 2020 ACTIVE
Intercollaborative Radiation Countermeasure Consortium (INTERACT Consortium) for advanced development of medical countermeasures (MCM) to mitigate/treat acute and delayed radiation syndromes
Role: Co-Investigator
Funding: UNIV OF MARYLAND COLLEGE PARK via NATL INST OF HLTH NIAID
Apr 2020 ACTIVE
Inhibition of Bcl-xL by Targeted Degradation
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Sep 2019 ACTIVE
Use of BCL-xL Proteolysis targeting chimeras to treat pancreatic cancer
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Aug 2019 ACTIVE
Develop BCL-xL proteolysis targeting chimeras as safer and better senolytics
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Sep 2018 – Feb 2020
Cancer Therapy-induced Long-term Bone Marrow Injury
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Sep 2018 – Aug 2020
NCI Clinical and Translational Exploratory/ Developmental Studies
Role: Co-Investigator
Funding: NATL INST OF HLTH NCI
Aug 2018 – Aug 2019
Discovery and Target Identification of Senolytic Agents
Role: Co-Investigator
Funding: NATL INST OF HLTH NIA
Jul 2018 ACTIVE
Role of Senescent Cells in Radiation-induced Pulmonary Fibrosis
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI
Jun 2018 – May 2019
The 4th International Cell Senescence Association (ICSA) meeting (ICSA 2018) Resubmission
Role: Principal Investigator
Funding: NATL INST OF HLTH NIA
Apr 2018 ACTIVE
Ionizing radiation induced hematological malignancies
Role: Principal Investigator
Funding: NATL INST OF HLTH NCI

Education

M.S.
1986 · Henan Medical University
M.D.
1982 · Yunyang Medical College

Teaching Profile

Courses Taught
2020-2021
PHA6512L Experiential Research Training in Pharmacodynamics
2019-2020
PHA7980 Research for Doctoral Dissertation
2020-2021
PHA6936 Advanced Topics in Pharmaceutical Sciences
2019-2021
PHA7979 Advanced Research
2020-2021
PHA6521C Research Techniques in Pharmacodynamics
2020
PHA6910 Supervised Research
2020-2021
GMS6691 Special Topics in Cell Biology and Anatomy
2020-2021
PHA5930 Sem Pharm Research

Contact Details

Phones:
Business:
(352) 294-8952
Emails: