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Charles  Chalfant

Charles Chalfant

Charles Chalfant
Professor and CMMB Chair

Contact

Office: ISA 2018E & 6206
Phone: 813/974-7103
Lab: ISA 6058
Fax: (813) 905-9919
Email:

Links

Education

  • B.S., 1992, University of Tampa
  • Ph.D., 1997, University of South Florida College of Medicine

Professional Experience

  • National Research Service Award, Postdoctoral Fellow, Duke University
  • Medical University of South Carolina, Advisor: Yusuf Hannun, M.D.

Research

The Chalfant laboratory is currently focused on two major areas of cell signaling and human pathophysiologies. Specifically, the laboratory focuses on: 1) lipid and oncogenic regulation of alternative splicing; and 2) the regulation of eicosanoid synthesis in inflammation and cancer. In regards to the former area, our laboratory focuses on the alternative splicing of caspase 9 and Bcl-x, major regulators of apoptosis and chemotherapy sensitivity of non-small cell lung cancer (NSCLC) cells. NSCLC represents the majority of lung cancers and carries a poor prognosis with a median survival of less than 12 months. Therefore, new strategies are needed in the treatment of NSCLC in order to impact this disease. In regards to caspase 9 RNA splicing and new NSCLC therapies, the expression of caspase 9 is regulated, in one aspect, by alternative RNA splicing via the inclusion or exclusion of an exonic cassette (exons 3, 4, 5, and 6). Inclusion of this exonic cassette into the mature transcript produces the pro-apoptotic caspase 9 (caspase 9a) while the exclusion produces the anti-apoptotic caspase 9, which is regulated by the production of the apoptotic lipid, ceramide. Studies from our laboratory have shown that the regulation of the inclusion of this four exon cassette is a critical factor in determining whether a cell is susceptible or resistant to apoptosis, and thus oncogenic transformation. Currently the laboratory is focused on determining the mechanism regulating caspase 9b formation as well as the downstream cell signaling modulated by this novel splice variant. The overall goal of the research is to determine whether this distal mechanism is a new target for anti-cancer therapeutics.

Our second line of research is also very exciting examining the biological function of a relatively new addition to bioactive sphingolipids, ceramide-1-phosphate (C1P). Specifically, we are examining the role of this bioactive lipid in inflammatory diseases (e.g. trauma-induced coagulopathy, sepsis, anaphylaxis) and cancer via regulation of eicosanoid biosynthesis. Sepsis, for example, is a term used to describe a severe illness arising from serious infection. The mortality rate of sepsis is >215,000 patients a year, and sepsis is the tenth leading cause of death in the US. As such, numerous clinical trials for the treatment of this disease have been undertaken, but unfortunately, these trials have shown limited success. Thus, there is a major need for new therapeutics to treat the disease. As for new therapeutics to combat this disease, products of arachidonic acid (AA), eicosanoids, are well-established mediators of inflammatory responses with major roles in the pathogenesis of the above disease states including sepsis. The production of AA by phospholipases is the initial rate-limiting step in eicosanoid biosynthesis, and the major phospholipase that regulates eicosanoid synthesis in response to inflammatory agonists is group IVA cytosolic phospholipase A2 (cPLA2α). The Chalfant laboratory was the first to demonstrate that C1P generated by ceramide kinase was a novel and specific activator of cPLA2α. Our recent findings also demonstrated that the specific interaction site for C1P is localized to the calcium binding loop II of the C2 domain of cPLA2α making our laboratory group the first to fully characterize a specific interaction site for a bioactive sphingolipid. The Chalfant laboratory also demonstrated that mutagenesis of critical amino acids for the C1P interaction inhibited the ability of cPLA2α to translocate in response to inflammatory agonists. Lastly, our new knockin mouse with this interaction site ablated is generating new insights as to how this lipid:protein interaction regulates the formation of bioactive lipids in vivo. Overall, our data are suggesting that the C1P/cPLA2α interaction is a new target for the development of a new generation of anti-inflammatory mediators, and this line of research is a major focus of the laboratory.

Ph.D. Students (VCU)

Daniel Stephenson
James “Tommy” Deligio
Patrick MacKnight

Undergraduate Researchers

Shanique Thompson
Daniel Paolillo
Brittany A. Dudley

Technical Support/Lab Manager

Christopher Cardona

Graduate Students

Anika Ali, Joao Paulo Costa Pinho, Dawn Moody, Robert Morris, Christina Moss

Recent Publications

NCBI Collection

1: Mishra SK, Gao YG, Deng Y, Chalfant CE, Hinchcliffe EH, Brown RE. CPTP: A
sphingolipid transfer protein that regulates autophagy and inflammasome
activation. Autophagy. 2017 Nov 22:1-46. doi: 10.1080/15548627.2017.1393129.
[Epub ahead of print] PubMed PMID: 29164996.

2: DeLigio JT, Lin G, Chalfant CE, Park MA. Splice variants of cytosolic
polyadenylation element-binding protein 2 (CPEB2) differentially regulate
pathways linked to cancer metastasis. J Biol Chem. 2017 Oct
27;292(43):17909-17918. doi: 10.1074/jbc.M117.810127. Epub 2017 Sep 13. PubMed
PMID: 28904175; PubMed Central PMCID: PMC5663888.

3: Stephenson DJ, Hoeferlin LA, Chalfant CE. Lipidomics in translational research
and the clinical significance of lipid-based biomarkers. Transl Res. 2017
Nov;189:13-29. doi: 10.1016/j.trsl.2017.06.006. Epub 2017 Jun 15. Review. PubMed
PMID: 28668521; PubMed Central PMCID: PMC5659874.

4: Mohammed BM, Sanford KW, Fisher BJ, Martin EJ, Contaifer D Jr, Warncke UO,
Wijesinghe DS, Chalfant CE, Brophy DF, Fowler Iii AA, Natarajan R. Impact of high
dose vitamin C on platelet function. World J Crit Care Med. 2017 Feb
4;6(1):37-47. doi: 10.5492/wjccm.v6.i1.37. eCollection 2017 Feb 4. PubMed PMID:
28224106; PubMed Central PMCID: PMC5295168.

5: Qi H, Priyadarsini S, Nicholas SE, Sarker-Nag A, Allegood J, Chalfant CE,
Mandal NA, Karamichos D. Analysis of sphingolipids in human corneal fibroblasts
from normal and keratoconus patients. J Lipid Res. 2017 Apr;58(4):636-648. doi:
10.1194/jlr.M067264. Epub 2017 Feb 10. PubMed PMID: 28188148; PubMed Central
PMCID: PMC5392739.

6: Vhuiyan MI, Pak ML, Park MA, Thomas D, Lakowski TM, Chalfant CE, Frankel A.
PRMT2 interacts with splicing factors and regulates the alternative splicing of
BCL-X. J Biochem. 2017 Jul 1;162(1):17-25. doi: 10.1093/jb/mvw102. PubMed PMID:
28057797.

7: Contaifer D Jr, Carl DE, Warncke UO, Martin EJ, Mohammed BM, Van Tassell B,
Brophy DF, Chalfant CE, Wijesinghe DS. Unsupervised analysis of combined lipid
and coagulation data reveals coagulopathy subtypes among dialysis patients. J
Lipid Res. 2017 Mar;58(3):586-599. doi: 10.1194/jlr.P068833. Epub 2016 Dec 19.
PubMed PMID: 27993949; PubMed Central PMCID: PMC5335589.

8: Shapiro BA, Vu NT, Shultz MD, Shultz JC, Mietla JA, Gouda MM, Yacoub A, Dent
P, Fisher PB, Park MA, Chalfant CE. Melanoma Differentiation-associated Gene
7/IL-24 Exerts Cytotoxic Effects by Altering the Alternative Splicing of Bcl-x
Pre-mRNA via the SRC/PKCd Signaling Axis. J Biol Chem. 2016 Oct
7;291(41):21669-21681. Epub 2016 Aug 12. PubMed PMID: 27519412; PubMed Central
PMCID: PMC5076836.

9: Vu NT, Park MA, Shultz MD, Bulut GB, Ladd AC, Chalfant CE. Caspase-9b
Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-?B
and Lung Tumorigenesis. Cancer Res. 2016 May 15;76(10):2977-89. doi:
10.1158/0008-5472.CAN-15-2512. Epub 2016 Mar 29. PubMed PMID: 27197231; PubMed
Central PMCID: PMC4874651.

10: McClure MJ, Clark NM, Hyzy SL, Chalfant CE, Olivares-Navarrete R, Boyan BD,
Schwartz Z. Role of integrin a7ß1 signaling in myoblast differentiation on
aligned polydioxanone scaffolds. Acta Biomater. 2016 Jul 15;39:44-54. doi:
10.1016/j.actbio.2016.04.046. Epub 2016 Apr 30. PubMed PMID: 27142254.

11: Stiles M, Qi H, Sun E, Tan J, Porter H, Allegood J, Chalfant CE, Yasumura D,
Matthes MT, LaVail MM, Mandal NA. Sphingolipid profile alters in retinal
dystrophic P23H-1 rats and systemic FTY720 can delay retinal degeneration. J
Lipid Res. 2016 May;57(5):818-31. doi: 10.1194/jlr.M063719. Epub 2016 Mar 5.
PubMed PMID: 26947037; PubMed Central PMCID: PMC4847629.

12: Kolawole EM, McLeod JJ, Ndaw V, Abebayehu D, Barnstein BO, Faber T, Spence
AJ, Taruselli M, Paranjape A, Haque TT, Qayum AA, Kazmi QA, Wijesinghe DS,
Sturgill JL, Chalfant CE, Straus DB, Oskeritzian CA, Ryan JJ. Fluvastatin
Suppresses Mast Cell and Basophil IgE Responses: Genotype-Dependent Effects. J
Immunol. 2016 Feb 15;196(4):1461-70. doi: 10.4049/jimmunol.1501932. Epub 2016 Jan
15. PubMed PMID: 26773154; PubMed Central PMCID: PMC4744515.

13: Katz S, Ernst O, Avni D, Athamna M, Philosoph A, Arana L, Ouro A, Hoeferlin
LA, Meijler MM, Chalfant CE, Gómez-Muñoz A, Zor T. Exogenous ceramide-1-phosphate
(C1P) and phospho-ceramide analogue-1 (PCERA-1) regulate key macrophage
activities via distinct receptors. Immunol Lett. 2016 Jan;169:73-81. doi:
10.1016/j.imlet.2015.12.001. Epub 2015 Dec 3. PubMed PMID: 26656944; PubMed
Central PMCID: PMC4837700.

14: Johnson RM, Vu NT, Griffin BP, Gentry AE, Archer KJ, Chalfant CE, Park MA.
The Alternative Splicing of Cytoplasmic Polyadenylation Element Binding Protein 2
Drives Anoikis Resistance and the Metastasis of Triple Negative Breast Cancer. J
Biol Chem. 2015 Oct 16;290(42):25717-27. doi: 10.1074/jbc.M115.671206. Epub 2015
Aug 24. PubMed PMID: 26304115; PubMed Central PMCID: PMC4646214.

15: Truchan HK, VieBrock L, Cockburn CL, Ojogun N, Griffin BP, Wijesinghe DS,
Chalfant CE, Carlyon JA. Anaplasma phagocytophilum Rab10-dependent parasitism of
the trans-Golgi network is critical for completion of the infection cycle. Cell
Microbiol. 2016 Feb;18(2):260-81. doi: 10.1111/cmi.12500. Epub 2015 Oct 7. PubMed
PMID: 26289115; PubMed Central PMCID: PMC4891814.

16: Dhall S, Wijesinghe DS, Karim ZA, Castro A, Vemana HP, Khasawneh FT, Chalfant
CE, Martins-Green M. Arachidonic acid-derived signaling lipids and functions in
impaired healing. Wound Repair Regen. 2015 Sep;23(5):644-56. doi:
10.1111/wrr.12337. Epub 2015 Sep 14. PubMed PMID: 26135854; PubMed Central PMCID:
PMC4837701.

17: Al-Husseini A, Wijesinghe DS, Farkas L, Kraskauskas D, Drake JI, Van Tassel
B, Abbate A, Chalfant CE, Voelkel NF. Increased eicosanoid levels in the
Sugen/chronic hypoxia model of severe pulmonary hypertension. PLoS One. 2015 Mar
18;10(3):e0120157. doi: 10.1371/journal.pone.0120157. eCollection 2015. PubMed
PMID: 25785937; PubMed Central PMCID: PMC4364907.

18: Barbour SE, Nguyen PT, Park M, Emani B, Lei X, Kambalapalli M, Shultz JC,
Wijesinghe D, Chalfant CE, Ramanadham S. Group VIA Phospholipase A2 (iPLA2ß)
Modulates Bcl-x 5'-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L)
in ß-Cells. J Biol Chem. 2015 Apr 24;290(17):11021-31. doi:
10.1074/jbc.M115.648956. Epub 2015 Mar 11. PubMed PMID: 25762722; PubMed Central
PMCID: PMC4409262.

19: Hoeferlin LA, Huynh QK, Mietla JA, Sell SA, Tucker J, Chalfant CE, Wijesinghe
DS. The Lipid Portion of Activated Platelet-Rich Plasma Significantly Contributes
to Its Wound Healing Properties. Adv Wound Care (New Rochelle). 2015 Feb
1;4(2):100-109. PubMed PMID: 25713752; PubMed Central PMCID: PMC4322089.

20: Dhall S, Do D, Garcia M, Wijesinghe DS, Brandon A, Kim J, Sanchez A,
Lyubovitsky J, Gallagher S, Nothnagel EA, Chalfant CE, Patel RP, Schiller N,
Martins-Green M. A novel model of chronic wounds: importance of redox imbalance
and biofilm-forming bacteria for establishment of chronicity. PLoS One. 2014 Oct
14;9(10):e109848. doi: 10.1371/journal.pone.0109848. eCollection 2014. PubMed
PMID: 25313558; PubMed Central PMCID: PMC4196950.

21: Mohammed BM, Fisher BJ, Huynh QK, Wijesinghe DS, Chalfant CE, Brophy DF,
Fowler AA 3rd, Natarajan R. Resolution of sterile inflammation: role for vitamin
C. Mediators Inflamm. 2014;2014:173403. doi: 10.1155/2014/173403. Epub 2014 Sep
9. PubMed PMID: 25294953; PubMed Central PMCID: PMC4175383.

22: Integrative HMP (iHMP) Research Network Consortium. The Integrative Human
Microbiome Project: dynamic analysis of microbiome-host omics profiles during
periods of human health and disease. Cell Host Microbe. 2014 Sep 10;16(3):276-89.
doi: 10.1016/j.chom.2014.08.014. PubMed PMID: 25211071; PubMed Central PMCID:
PMC5109542.

23: Wijesinghe DS, Brentnall M, Mietla JA, Hoeferlin LA, Diegelmann RF, Boise LH,
Chalfant CE. Ceramide kinase is required for a normal eicosanoid response and the
subsequent orderly migration of fibroblasts. J Lipid Res. 2014
Jul;55(7):1298-309. doi: 10.1194/jlr.M048207. Epub 2014 May 13. PubMed PMID:
24823941; PubMed Central PMCID: PMC4076082.

24: Shaak TL, Wijesinghe DS, Chalfant CE, Diegelmann RF, Ward KR, Loria RM.
Structural Stereochemistry of Androstene Hormones Determines Interactions with
Human Androgen, Estrogen, and Glucocorticoid Receptors. Int J Med Chem. 2013 Mar
14;2013:203606. PubMed PMID: 24729874; PubMed Central PMCID: PMC3981456.

25: van den Elsen LW, Spijkers LJ, van den Akker RF, van Winssen AM, Balvers M,
Wijesinghe DS, Chalfant CE, Garssen J, Willemsen LE, Alewijnse AE, Peters SL.
Dietary fish oil improves endothelial function and lowers blood pressure via
suppression of sphingolipid-mediated contractions in spontaneously hypertensive
rats. J Hypertens. 2014 May;32(5):1050-8; discussion 1058. doi:
10.1097/HJH.0000000000000131. PubMed PMID: 24569415; PubMed Central PMCID:
PMC4312004.

26: Wijesinghe DS, Chalfant CE. Systems-Level Lipid Analysis Methodologies for
Qualitative and Quantitative Investigation of Lipid Signaling Events During Wound
Healing. Adv Wound Care (New Rochelle). 2013 Nov;2(9):538-548. PubMed PMID:
24527363; PubMed Central PMCID: PMC3816989.

27: Simanshu DK, Kamlekar RK, Wijesinghe DS, Zou X, Zhai X, Mishra SK,
Molotkovsky JG, Malinina L, Hinchcliffe EH, Chalfant CE, Brown RE, Patel DJ.
Non-vesicular trafficking by a ceramide-1-phosphate transfer protein regulates
eicosanoids. Nature. 2013 Aug 22;500(7463):463-7. doi: 10.1038/nature12332. Epub
2013 Jul 17. PubMed PMID: 23863933; PubMed Central PMCID: PMC3951269.

28: West NW, Garcia-Vargas A, Chalfant CE, Park MA. OSU-03012 sensitizes breast
cancers to lapatinib-induced cell killing: a role for Nck1 but not Nck2. BMC
Cancer. 2013 May 24;13:256. doi: 10.1186/1471-2407-13-256. PubMed PMID: 23706161;
PubMed Central PMCID: PMC3674920.

29: Khanna S, Rink C, Ghoorkhanian R, Gnyawali S, Heigel M, Wijesinghe DS,
Chalfant CE, Chan YC, Banerjee J, Huang Y, Roy S, Sen CK. Loss of miR-29b
following acute ischemic stroke contributes to neural cell death and infarct
size. J Cereb Blood Flow Metab. 2013 Aug;33(8):1197-206. doi:
10.1038/jcbfm.2013.68. Epub 2013 May 1. PubMed PMID: 23632968; PubMed Central
PMCID: PMC3734770.

30: Hoeferlin LA, Wijesinghe DS, Chalfant CE. The role of ceramide-1-phosphate in
biological functions. Handb Exp Pharmacol. 2013;(215):153-66. doi:
10.1007/978-3-7091-1368-4_8. Review. PubMed PMID: 23579454; PubMed Central PMCID:
PMC5598467.

31: Mietla JA, Wijesinghe DS, Hoeferlin LA, Shultz MD, Natarajan R, Fowler AA
3rd, Chalfant CE. Characterization of eicosanoid synthesis in a genetic ablation
model of ceramide kinase. J Lipid Res. 2013 Jul;54(7):1834-47. doi:
10.1194/jlr.M035683. Epub 2013 Apr 10. PubMed PMID: 23576683; PubMed Central
PMCID: PMC3679386.

32: Vu NT, Park MA, Shultz JC, Goehe RW, Hoeferlin LA, Shultz MD, Smith SA, Lynch
KW, Chalfant CE. hnRNP U enhances caspase-9 splicing and is modulated by
AKT-dependent phosphorylation of hnRNP L. J Biol Chem. 2013 Mar
22;288(12):8575-84. doi: 10.1074/jbc.M112.443333. Epub 2013 Feb 8. PubMed PMID:
23396972; PubMed Central PMCID: PMC3605676.

33: Ward KE, Bhardwaj N, Vora M, Chalfant CE, Lu H, Stahelin RV. The molecular
basis of ceramide-1-phosphate recognition by C2 domains. J Lipid Res. 2013
Mar;54(3):636-48. doi: 10.1194/jlr.M031088. Epub 2012 Dec 31. PubMed PMID:
23277511; PubMed Central PMCID: PMC3617939.

34: Gomez-Arroyo J, Mizuno S, Szczepanek K, Van Tassell B, Natarajan R, dos
Remedios CG, Drake JI, Farkas L, Kraskauskas D, Wijesinghe DS, Chalfant CE,
Bigbee J, Abbate A, Lesnefsky EJ, Bogaard HJ, Voelkel NF. Metabolic gene
remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy
secondary to pulmonary arterial hypertension. Circ Heart Fail. 2013
Jan;6(1):136-44. doi: 10.1161/CIRCHEARTFAILURE.111.966127. Epub 2012 Nov 14.
PubMed PMID: 23152488; PubMed Central PMCID: PMC3790960.

35: Wilson JD, Broaddus WC, Dorn HC, Fatouros PP, Chalfant CE, Shultz MD.
Metallofullerene-nanoplatform-delivered interstitial brachytherapy improved
survival in a murine model of glioblastoma multiforme. Bioconjug Chem. 2012 Sep
19;23(9):1873-80. Epub 2012 Aug 21. PubMed PMID: 22881865; PubMed Central PMCID:
PMC3448337.

36: Shultz JC, Vu N, Shultz MD, Mba MU, Shapiro BA, Chalfant CE. The
Proto-oncogene PKC? regulates the alternative splicing of Bcl-x pre-mRNA. Mol
Cancer Res. 2012 May;10(5):660-9. doi: 10.1158/1541-7786.MCR-11-0363. Epub 2012
Apr 20. PubMed PMID: 22522453; PubMed Central PMCID: PMC3356487.

37: Shultz JC, Chalfant CE. The flip-flop HuR: part of the problem or the
solution in fighting cancer? J Clin Invest. 2012 Jan;122(1):16-9. doi:
10.1172/JCI61677. Epub 2011 Dec 27. PubMed PMID: 22201677; PubMed Central PMCID:
PMC3248312.

38: Spijkers LJ, Janssen BJ, Nelissen J, Meens MJ, Wijesinghe D, Chalfant CE, De
Mey JG, Alewijnse AE, Peters SL. Antihypertensive treatment differentially
affects vascular sphingolipid biology in spontaneously hypertensive rats. PLoS
One. 2011;6(12):e29222. doi: 10.1371/journal.pone.0029222. Epub 2011 Dec 15.
PubMed PMID: 22195025; PubMed Central PMCID: PMC3240660.

39: Wijesinghe DS, Mayton EK, Mietla JA, Mukherjee A, Wu J, Fang X, Chalfant CE.
Characterization of lysophosphatidic acid subspecies produced by autotaxin using
a modified HPLC ESI-MS/MS method. Anal Methods. 2011 Nov 1;3(12):2822-2828.
PubMed PMID: 24648853; PubMed Central PMCID: PMC3956132.

40: Lamour NF, Wijesinghe DS, Mietla JA, Ward KE, Stahelin RV, Chalfant CE.
Ceramide kinase regulates the production of tumor necrosis factor a (TNFa) via
inhibition of TNFa-converting enzyme. J Biol Chem. 2011 Dec 16;286(50):42808-17.
doi: 10.1074/jbc.M111.310169. Epub 2011 Oct 18. PubMed PMID: 22009748; PubMed
Central PMCID: PMC3234830.

41: Lamour NF, Wijesinghe DS, Mietla JA, Ward KE, Stahelin RV, Chalfant CE.
WITHDRAWN: Ceramide kinase regulates the production of TNF{alpha} via inhibition
of TNF{alpha}-converting enzyme. J Biol Chem. 2011 Sep 27. [Epub ahead of print]
PubMed PMID: 21896476.

42: Spijkers LJ, van den Akker RF, Janssen BJ, Debets JJ, De Mey JG, Stroes ES,
van den Born BJ, Wijesinghe DS, Chalfant CE, MacAleese L, Eijkel GB, Heeren RM,
Alewijnse AE, Peters SL. Hypertension is associated with marked alterations in
sphingolipid biology: a potential role for ceramide. PLoS One. 2011;6(7):e21817.
doi: 10.1371/journal.pone.0021817. Epub 2011 Jul 19. PubMed PMID: 21818267;
PubMed Central PMCID: PMC3139577.

43: Shultz JC, Goehe RW, Murudkar CS, Wijesinghe DS, Mayton EK, Massiello A,
Hawkins AJ, Mukerjee P, Pinkerman RL, Park MA, Chalfant CE. SRSF1 regulates the
alternative splicing of caspase 9 via a novel intronic splicing enhancer
affecting the chemotherapeutic sensitivity of non-small cell lung cancer cells.
Mol Cancer Res. 2011 Jul;9(7):889-900. doi: 10.1158/1541-7786.MCR-11-0061. Epub
2011 May 26. PubMed PMID: 21622622; PubMed Central PMCID: PMC3140550.

44: Shultz JC, Chalfant CE. Caspase 9b: a new target for therapy in
non-small-cell lung cancer. Expert Rev Anticancer Ther. 2011 Apr;11(4):499-502.
doi: 10.1586/era.11.23. Review. PubMed PMID: 21504315.

45: Shultz JC, Goehe RW, Wijesinghe DS, Murudkar C, Hawkins AJ, Shay JW, Minna
JD, Chalfant CE. Alternative splicing of caspase 9 is modulated by the
phosphoinositide 3-kinase/Akt pathway via phosphorylation of SRp30a. Cancer Res.
2010 Nov 15;70(22):9185-96. doi: 10.1158/0008-5472.CAN-10-1545. Epub 2010 Nov 2.
PubMed PMID: 21045158; PubMed Central PMCID: PMC3059118.

46: Goldsmith M, Daka A, Lamour NF, Mashiach R, Glucksam Y, Meijler MM, Chalfant
CE, Zor T. A ceramide analog inhibits cPLA(2) activity and consequent PGE(2)
formation in LPS-stimulated macrophages. Immunol Lett. 2011 Mar
30;135(1-2):136-43. doi: 10.1016/j.imlet.2010.10.014. Epub 2010 Oct 30. PubMed
PMID: 21040745; PubMed Central PMCID: PMC3026855.

47: Goehe RW, Shultz JC, Murudkar C, Usanovic S, Lamour NF, Massey DH, Zhang L,
Camidge DR, Shay JW, Minna JD, Chalfant CE. hnRNP L regulates the tumorigenic
capacity of lung cancer xenografts in mice via caspase-9 pre-mRNA processing. J
Clin Invest. 2010 Nov;120(11):3923-39. doi: 10.1172/JCI43552. Epub 2010 Oct 25.
PubMed PMID: 20972334; PubMed Central PMCID: PMC2964989.

48: Raucci FJ Jr, Wijesinghe DS, Chalfant CE, Baumgarten CM. Exogenous and
endogenous ceramides elicit volume-sensitive chloride current in ventricular
myocytes. Cardiovasc Res. 2010 Apr 1;86(1):55-62. doi: 10.1093/cvr/cvp399. Epub
2009 Dec 14. PubMed PMID: 20008476; PubMed Central PMCID: PMC2836262.

49: Gubern A, Barceló-Torns M, Barneda D, López JM, Masgrau R, Picatoste F,
Chalfant CE, Balsinde J, Balboa MA, Claro E. JNK and ceramide kinase govern the
biogenesis of lipid droplets through activation of group IVA phospholipase A2. J
Biol Chem. 2009 Nov 20;284(47):32359-69. doi: 10.1074/jbc.M109.061515. Epub 2009
Sep 24. PubMed PMID: 19778898; PubMed Central PMCID: PMC2781651.

50: Wijesinghe DS, Allegood JC, Gentile LB, Fox TE, Kester M, Chalfant CE. Use of
high performance liquid chromatography-electrospray ionization-tandem mass
spectrometry for the analysis of ceramide-1-phosphate levels. J Lipid Res. 2010
Mar;51(3):641-51. doi: 10.1194/jlr.D000430. Epub 2009 Aug 4. PubMed PMID:
19654423; PubMed Central PMCID: PMC2817594.

51: Lamour NF, Subramanian P, Wijesinghe DS, Stahelin RV, Bonventre JV, Chalfant
CE. Ceramide 1-phosphate is required for the translocation of group IVA cytosolic
phospholipase A2 and prostaglandin synthesis. J Biol Chem. 2009 Sep
25;284(39):26897-907. doi: 10.1074/jbc.M109.001677. Epub 2009 Jul 23. PubMed
PMID: 19632995; PubMed Central PMCID: PMC2785377.

52: Wijesinghe DS, Subramanian P, Lamour NF, Gentile LB, Granado MH, Bielawska A,
Szulc Z, Gomez-Munoz A, Chalfant CE. Chain length specificity for activation of
cPLA2alpha by C1P: use of the dodecane delivery system to determine
lipid-specific effects. J Lipid Res. 2009 Oct;50(10):1986-95. doi:
10.1194/jlr.M800367-JLR200. Epub 2008 Dec 15. PubMed PMID: 19075030; PubMed
Central PMCID: PMC2739767.

53: Lamour NF, Chalfant CE. Ceramide kinase and the
ceramide-1-phosphate/cPLA2alpha interaction as a therapeutic target. Curr Drug
Targets. 2008 Aug;9(8):674-82. Review. PubMed PMID: 18691014.

54: Shultz JC, Chalfant CE. Emetine and the alternative splicing of Bcl-X: where
to next? Chem Biol. 2007 Dec;14(12):1313-4. PubMed PMID: 18096499.

55: Wijesinghe DS, Lamour NF, Gomez-Munoz A, Chalfant CE. Ceramide kinase and
ceramide-1-phosphate. Methods Enzymol. 2007;434:265-92. PubMed PMID: 17954253.

56: Subramanian P, Vora M, Gentile LB, Stahelin RV, Chalfant CE. Anionic lipids
activate group IVA cytosolic phospholipase A2 via distinct and separate
mechanisms. J Lipid Res. 2007 Dec;48(12):2701-8. Epub 2007 Sep 21. PubMed PMID:
17890681.

57: Stahelin RV, Subramanian P, Vora M, Cho W, Chalfant CE. Ceramide-1-phosphate
binds group IVA cytosolic phospholipase a2 via a novel site in the C2 domain. J
Biol Chem. 2007 Jul 13;282(28):20467-74. Epub 2007 Apr 30. PubMed PMID: 17472963.

58: Lamour NF, Stahelin RV, Wijesinghe DS, Maceyka M, Wang E, Allegood JC,
Merrill AH Jr, Cho W, Chalfant CE. Ceramide kinase uses ceramide provided by
ceramide transport protein: localization to organelles of eicosanoid synthesis. J
Lipid Res. 2007 Jun;48(6):1293-304. Epub 2007 Mar 27. PubMed PMID: 17392267.

59: Paronetto MP, Achsel T, Massiello A, Chalfant CE, Sette C. The RNA-binding
protein Sam68 modulates the alternative splicing of Bcl-x. J Cell Biol. 2007 Mar
26;176(7):929-39. Epub 2007 Mar 19. PubMed PMID: 17371836; PubMed Central PMCID:
PMC2064079.

60: Mitra P, Maceyka M, Payne SG, Lamour N, Milstien S, Chalfant CE, Spiegel S.
Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma
cells. FEBS Lett. 2007 Feb 20;581(4):735-40. Epub 2007 Jan 25. PubMed PMID:
17274985.

61: Ghosh N, Patel N, Jiang K, Watson JE, Cheng J, Chalfant CE, Cooper DR.
Ceramide-activated protein phosphatase involvement in insulin resistance via Akt,
serine/arginine-rich protein 40, and ribonucleic acid splicing in L6 skeletal
muscle cells. Endocrinology. 2007 Mar;148(3):1359-66. Epub 2006 Dec 7. PubMed
PMID: 17158207; PubMed Central PMCID: PMC2664306.

62: Payne SG, Oskeritzian CA, Griffiths R, Subramanian P, Barbour SE, Chalfant
CE, Milstien S, Spiegel S. The immunosuppressant drug FTY720 inhibits cytosolic
phospholipase A2 independently of sphingosine-1-phosphate receptors. Blood. 2007
Feb 1;109(3):1077-85. Epub 2006 Sep 28. PubMed PMID: 17008548; PubMed Central
PMCID: PMC1785128.

63: Massiello A, Roesser JR, Chalfant CE. SAP155 Binds to ceramide-responsive RNA
cis-element 1 and regulates the alternative 5' splice site selection of Bcl-x
pre-mRNA. FASEB J. 2006 Aug;20(10):1680-2. Epub 2006 Jun 21. PubMed PMID:
16790528.

64: Kim WS, Chalfant CE, Garner B. Fine tuning therapeutic targeting of the
sphingolipid biosynthetic pathway to treat atherosclerosis. Curr Vasc Pharmacol.
2006 Apr;4(2):151-4. Review. PubMed PMID: 16611156.

65: Massiello A, Chalfant CE. SRp30a (ASF/SF2) regulates the alternative splicing
of caspase-9 pre-mRNA and is required for ceramide-responsiveness. J Lipid Res.
2006 May;47(5):892-7. Epub 2006 Feb 27. PubMed PMID: 16505493.

66: Lamour NF, Chalfant CE. Ceramide-1-phosphate: the "missing" link in
eicosanoid biosynthesis and inflammation. Mol Interv. 2005 Dec;5(6):358-67.
Review. PubMed PMID: 16394251.

67: Kanj SS, Dandashi N, El-Hed A, Harik H, Maalouf M, Kozhaya L, Mousallem T,
Tollefson AE, Wold WS, Chalfant CE, Dbaibo GS. Ceramide regulates SR protein
phosphorylation during adenoviral infection. Virology. 2006 Feb 5;345(1):280-9.
Epub 2005 Nov 3. PubMed PMID: 16271740.

68: Chalfant CE, Spiegel S. Sphingosine 1-phosphate and ceramide 1-phosphate:
expanding roles in cell signaling. J Cell Sci. 2005 Oct 15;118(Pt 20):4605-12.
Review. PubMed PMID: 16219683.

69: Wijesinghe DS, Massiello A, Subramanian P, Szulc Z, Bielawska A, Chalfant CE.
Substrate specificity of human ceramide kinase. J Lipid Res. 2005
Dec;46(12):2706-16. Epub 2005 Sep 18. PubMed PMID: 16170208.

70: Pettus BJ, Kitatani K, Chalfant CE, Taha TA, Kawamori T, Bielawski J, Obeid
LM, Hannun YA. The coordination of prostaglandin E2 production by
sphingosine-1-phosphate and ceramide-1-phosphate. Mol Pharmacol. 2005
Aug;68(2):330-5. Epub 2005 May 17. PubMed PMID: 15900018.

71: Subramanian P, Stahelin RV, Szulc Z, Bielawska A, Cho W, Chalfant CE.
Ceramide 1-phosphate acts as a positive allosteric activator of group IVA
cytosolic phospholipase A2 alpha and enhances the interaction of the enzyme with
phosphatidylcholine. J Biol Chem. 2005 May 6;280(18):17601-7. Epub 2005 Mar 1.
PubMed PMID: 15743759.

72: Pettus BJ, Chalfant CE, Hannun YA. Sphingolipids in inflammation: roles and
implications. Curr Mol Med. 2004 Jun;4(4):405-18. Review. PubMed PMID: 15354871.

73: Patel NA, Apostolatos HS, Mebert K, Chalfant CE, Watson JE, Pillay TS, Sparks
J, Cooper DR. Insulin regulates protein kinase CbetaII alternative splicing in
multiple target tissues: development of a hormonally responsive heterologous
minigene. Mol Endocrinol. 2004 Apr;18(4):899-911. Epub 2004 Jan 29. PubMed PMID:
14752056.

74: Massiello A, Salas A, Pinkerman RL, Roddy P, Roesser JR, Chalfant CE.
Identification of two RNA cis-elements that function to regulate the 5' splice
site selection of Bcl-x pre-mRNA in response to ceramide. J Biol Chem. 2004 Apr
16;279(16):15799-804. Epub 2004 Jan 20. PubMed PMID: 14734550.

75: Pettus BJ, Bielawska A, Subramanian P, Wijesinghe DS, Maceyka M, Leslie CC,
Evans JH, Freiberg J, Roddy P, Hannun YA, Chalfant CE. Ceramide 1-phosphate is a
direct activator of cytosolic phospholipase A2. J Biol Chem. 2004 Mar
19;279(12):11320-6. Epub 2003 Dec 15. PubMed PMID: 14676210.

76: Chalfant CE, Szulc Z, Roddy P, Bielawska A, Hannun YA. The structural
requirements for ceramide activation of serine-threonine protein phosphatases. J
Lipid Res. 2004 Mar;45(3):496-506. Epub 2003 Dec 1. PubMed PMID: 14657198.

77: Pettus BJ, Bielawski J, Porcelli AM, Reames DL, Johnson KR, Morrow J,
Chalfant CE, Obeid LM, Hannun YA. The sphingosine kinase
1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in
response to TNF-alpha. FASEB J. 2003 Aug;17(11):1411-21. PubMed PMID: 12890694.

78: Pettus BJ, Bielawska A, Spiegel S, Roddy P, Hannun YA, Chalfant CE. Ceramide
kinase mediates cytokine- and calcium ionophore-induced arachidonic acid release.
J Biol Chem. 2003 Oct 3;278(40):38206-13. Epub 2003 Jul 10. PubMed PMID:
12855693.

79: Pettus BJ, Chalfant CE, Hannun YA. Ceramide in apoptosis: an overview and
current perspectives. Biochim Biophys Acta. 2002 Dec 30;1585(2-3):114-25. Review.
PubMed PMID: 12531544.

80: Patel NA, Eichler DC, Chappell DS, Illingworth PA, Chalfant CE, Yamamoto M,
Dean NM, Wyatt JR, Mebert K, Watson JE, Cooper DR. The protein kinase C beta II
exon confers mRNA instability in the presence of high glucose concentrations. J
Biol Chem. 2003 Jan 10;278(2):1149-57. Epub 2002 Oct 28. PubMed PMID: 12407109.

81: Jenkins GM, Cowart LA, Signorelli P, Pettus BJ, Chalfant CE, Hannun YA. Acute
activation of de novo sphingolipid biosynthesis upon heat shock causes an
accumulation of ceramide and subsequent dephosphorylation of SR proteins. J Biol
Chem. 2002 Nov 8;277(45):42572-8. Epub 2002 Aug 27. PubMed PMID: 12200446.

82: Chalfant CE, Rathman K, Pinkerman RL, Wood RE, Obeid LM, Ogretmen B, Hannun
YA. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in
A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem.
2002 Apr 12;277(15):12587-95. Epub 2002 Jan 18. PubMed PMID: 11801602.

83: Chalfant CE, Ogretmen B, Galadari S, Kroesen BJ, Pettus BJ, Hannun YA. FAS
activation induces dephosphorylation of SR proteins; dependence on the de novo
generation of ceramide and activation of protein phosphatase 1. J Biol Chem. 2001
Nov 30;276(48):44848-55. Epub 2001 Aug 13. PubMed PMID: 11502750.

84: Patel NA, Chalfant CE, Watson JE, Wyatt JR, Dean NM, Eichler DC, Cooper DR.
Insulin regulates alternative splicing of protein kinase C beta II through a
phosphatidylinositol 3-kinase-dependent pathway involving the nuclear
serine/arginine-rich splicing factor, SRp40, in skeletal muscle cells. J Biol
Chem. 2001 Jun 22;276(25):22648-54. Epub 2001 Mar 30. PubMed PMID: 11283022.

85: Chalfant CE, Kishikawa K, Bielawska A, Hannun YA. Analysis of
ceramide-activated protein phosphatases. Methods Enzymol. 2000;312:420-8. PubMed
PMID: 11070890.

86: Yamamoto M, Acevedo-Duncan M, Chalfant CE, Patel NA, Watson JE, Cooper DR.
Acute glucose-induced downregulation of PKC-betaII accelerates cultured VSMC
proliferation. Am J Physiol Cell Physiol. 2000 Sep;279(3):C587-95. PubMed PMID:
10942708.

87: Chalfant CE, Ciaraldi TP, Watson JE, Nikoulina S, Henry RR, Cooper DR.
Protein kinase Ctheta expression is increased upon differentiation of human
skeletal muscle cells: dysregulation in type 2 diabetic patients and a possible
role for protein kinase Ctheta in insulin-stimulated glycogen synthase activity.
Endocrinology. 2000 Aug;141(8):2773-8. PubMed PMID: 10919262.

88: Cooper DR, Watson JE, Patel N, Illingworth P, Acevedo-Duncan M, Goodnight J,
Chalfant CE, Mischak H. Ectopic expression of protein kinase CbetaII, -delta, and
-epsilon, but not -betaI or -zeta, provide for insulin stimulation of glucose
uptake in NIH-3T3 cells. Arch Biochem Biophys. 1999 Dec 1;372(1):69-79. Erratum
in: Arch Biochem Biophys 2001 Apr 1;388(1):178. PubMed PMID: 10562418.

89: Kishikawa K, Chalfant CE, Perry DK, Bielawska A, Hannun YA. Phosphatidic acid
is a potent and selective inhibitor of protein phosphatase 1 and an inhibitor of
ceramide-mediated responses. J Biol Chem. 1999 Jul 23;274(30):21335-41. PubMed
PMID: 10409693.

90: Chalfant CE, Kishikawa K, Mumby MC, Kamibayashi C, Bielawska A, Hannun YA.
Long chain ceramides activate protein phosphatase-1 and protein phosphatase-2A.
Activation is stereospecific and regulated by phosphatidic acid. J Biol Chem.
1999 Jul 16;274(29):20313-7. PubMed PMID: 10400653.

91: Patel NA, Chalfant CE, Yamamoto M, Watson JE, Eichler DC, Cooper DR. Acute
hyperglycemia regulates transcription and posttranscriptional stability of
PKCbetaII mRNA in vascular smooth muscle cells. FASEB J. 1999 Jan;13(1):103-13.
PubMed PMID: 9872935.

92: Yamamoto M, Acevedo-Duncan M, Chalfant CE, Patel NA, Watson JE, Cooper DR.
The roles of protein kinase C beta I and beta II in vascular smooth muscle cell
proliferation. Exp Cell Res. 1998 May 1;240(2):349-58. PubMed PMID: 9597008.

93: Chalfant CE, Watson JE, Bisnauth LD, Kang JB, Patel N, Obeid LM, Eichler DC,
Cooper DR. Insulin regulates protein kinase CbetaII expression through enhanced
exon inclusion in L6 skeletal muscle cells. A novel mechanism of insulin- and
insulin-like growth factor-i-induced 5' splice site selection. J Biol Chem. 1998
Jan 9;273(2):910-6. PubMed PMID: 9422749.

94: Chalfant CE, Ohno S, Konno Y, Fisher AA, Bisnauth LD, Watson JE, Cooper DR. A
carboxy-terminal deletion mutant of protein kinase C beta II inhibits
insulin-stimulated 2-deoxyglucose uptake in L6 rat skeletal muscle cells. Mol
Endocrinol. 1996 Oct;10(10):1273-81. PubMed PMID: 9121494.

95: Coulson R, Proch PS, Olsson RA, Chalfant CE, Cooper DR. Upregulated renal
adenosine A1 receptors augment PKC and glucose transport but inhibit
proliferation. Am J Physiol. 1996 Feb;270(2 Pt 2):F263-74. PubMed PMID: 8779886.

96: Acevedo-Duncan M, Collins J, Zhang R, Haller E, Chalfant CE, Cooper DR. In
situ effects of interferon on human glioma protein kinase C-alpha and -beta
ultrastructural localization. Cell Growth Differ. 1995 Nov;6(11):1353-65. PubMed
PMID: 8562473.

97: Chalfant CE, Mischak H, Watson JE, Winkler BC, Goodnight J, Farese RV, Cooper
DR. Regulation of alternative splicing of protein kinase C beta by insulin. J
Biol Chem. 1995 Jun 2;270(22):13326-32. PubMed PMID: 7768933.

98: Gower WR Jr, Dietz JR, Vesely DL, Finley CL, Skolnick KA, Fabri PJ, Cooper
DR, Chalfant CE. Atrial natriuretic peptide gene expression in the rat
gastrointestinal tract. Biochem Biophys Res Commun. 1994 Jul 15;202(1):562-70.
PubMed PMID: 8037763.