Julian F. Hillyer, Ph.D.



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Faculty Appointments
Director of the Program in Career Development Professor of Biological Sciences Centennial Professor of Biological Sciences
Ph.D., Vector Biology, University of Wisconsin, Madison, WisconsinM.S., Veterinary Science, University of Wisconsin, Madison, WisconsinB.A., Biology, University of Chicago, Chicago, Illinois
Office Address
Vanderbilt University
Department of Biological Sciences

VU Station B, 35-1634

Nashville, TN 37235-1634
Research Description
Mosquitoes are cosmopolitan pests and disease vectors. For the completion of their life cycle, females of all anautogenous species are required to take a blood meal for the production of eggs. Blood feeding can cause irritation in mammals and can potentially lead to the transmission of deadly and debilitating pathogens such as <i>Plasmodium falciparum</i> (malaria), <i>Wuchereria bancrofti</i> (lymphatic filariasis), dengue fever virus, and West Nile virus. To date, the control of mosquitoes and mosquito-borne diseases has consisted of killing the mosquito using chemical or biological agents, using drugs to treat infected individuals, and limiting vector-human contact. Although these approaches have reduced mosquito populations and disease prevalence in certain regions, their effectiveness is rapidly diminishing. Primary reasons for this include the emergence of insecticide resistance in mosquitoes and drug resistance by pathogens. Hence, because of the diminishing efficacy of current control methods, compounded by the failure to discover new insecticide replacements, drugs, and effective vaccines, it has become necessary to develop new control strategies.

The Hillyer Lab is interested in basic aspects of mosquito immunology and physiology, focusing on the mechanical and molecular bases of hemolymph (blood) propulsion, and the immunological interaction between mosquitoes and pathogens in the hemocoel (body cavity). Given that chemical and biological insecticides function in the mosquito hemocoel, and that disease-causing pathogens traverse this compartment prior to being transmitted, we expect that our research will contribute to the development of novel pest and disease control methods.

For more information, visit my lab webpage (http://www.vanderbilt.edu/hillyerlab/).
Research Keywords
Mosquito immunology and physiology; host-parasite interactions.
Brown LD, Shapiro LLM, Thompson GA, Estévez-Lao TY, Hillyer JF. Transstadial immune activation in a mosquito: Adults that emerge from infected larvae have stronger antibacterial activity in their hemocoel yet increased susceptibility to malaria infection. Ecol Evol. 2019 May; 9(10): 6082-95. PMID: 31161020, PMCID: PMC6540708, PII: ECE35192, DOI: 10.1002/ece3.5192, ISSN: 2045-7758.

Yan Y, Hillyer JF. Complement-like proteins TEP1, TEP3 and TEP4 are positive regulators of periostial hemocyte aggregation in the mosquito Anopheles gambiae. Insect Biochem. Mol. Biol [print-electronic]. 2019 Apr; 107: 1-9. PMID: 30690067, PII: S0965-1748(18)30470-3, DOI: 10.1016/j.ibmb.2019.01.007, ISSN: 1879-0240.

Hillyer JF. Presentation of the 2018 ASP Distinguished Service Award to Dennis J. Minchella. J. Parasitol [print-electronic]. 2018 Dec; 104(6): 601-2. PMID: 30011243, DOI: 10.1645/18-97, ISSN: 1937-2345.

Hillyer JF. Insect heart rhythmicity is modulated by evolutionarily conserved neuropeptides and neurotransmitters. Curr Opin Insect Sci [print-electronic]. 2018 Oct; 29: 41-8. PMID: 30551824, PII: S2214-5745(17)30212-2, DOI: 10.1016/j.cois.2018.06.002, ISSN: 2214-5753.

Sigle LT, Hillyer JF. Eater and draper are involved in the periostial haemocyte immune response in the mosquito Anopheles gambiae. Insect Mol. Biol [print-electronic]. 2018 Aug; 27(4): 429-38. PMID: 29520896, DOI: 10.1111/imb.12383, ISSN: 1365-2583.

Sigle LT, Hillyer JF. Structural and functional characterization of the contractile aorta and associated hemocytes of the mosquito Anopheles gambiae. J. Exp. Biol. 2018 Jun 6/22/2018; 221(Pt 12): PMID: 29724775, PII: jeb.181107, DOI: 10.1242/jeb.181107, ISSN: 1477-9145.

Sigle LT, Hillyer JF. Mosquito Hemocytes Associate With Circulatory Structures That Support Intracardiac Retrograde Hemolymph Flow. Front Physiol. 2018; 9: 1187. PMID: 30210361, PMCID: PMC6121077, DOI: 10.3389/fphys.2018.01187, ISSN: 1664-042X.

Brown LD, Thompson GA, Hillyer JF. Transstadial transmission of larval hemocoelic infection negatively affects development and adult female longevity in the mosquito Anopheles gambiae. J. Invertebr. Pathol [print-electronic]. 2018 Jan; 151: 21-31. PMID: 29111355, PMCID: PMC5801169, PII: S0022-2011(17)30350-6, DOI: 10.1016/j.jip.2017.10.008, ISSN: 1096-0805.

League GP, Estévez-Lao TY, Yan Y, Garcia-Lopez VA, Hillyer JF. Anopheles gambiae larvae mount stronger immune responses against bacterial infection than adults: evidence of adaptive decoupling in mosquitoes. Parasit Vectors. 2017 Aug 8/1/2017; 10(1): 367. PMID: 28764812, PMCID: PMC5539753, PII: 10.1186/s13071-017-2302-6, DOI: 10.1186/s13071-017-2302-6, ISSN: 1756-3305.

Doran CR, Estévez-Lao TY, Hillyer JF. Mosquito aging modulates the heart rate and the proportional directionality of heart contractions. J. Insect Physiol [print-electronic]. 2017 Aug; 101: 47-56. PMID: 28655496, PII: S0022-1910(17)30183-X, DOI: 10.1016/j.jinsphys.2017.06.013, ISSN: 1879-1611.

Chintapalli RT, Hillyer JF. Hemolymph circulation in insect flight appendages: physiology of the wing heart and circulatory flow in the wings of the mosquito Anopheles gambiae. J. Exp. Biol [print-electronic]. 2016 Dec 12/15/2016; 219(Pt 24): 3945-51. PMID: 27742896, PII: jeb.148254, DOI: 10.1242/jeb.148254, ISSN: 1477-9145.

Hillyer JF. George V. Hillyer (1943-2015). J. Parasitol [print-electronic]. 2016 Dec; 102(6): 659-61. PMID: 27553686, DOI: 10.1645/16-110, ISSN: 1937-2345.

League GP, Hillyer JF. Functional integration of the circulatory, immune, and respiratory systems in mosquito larvae: pathogen killing in the hemocyte-rich tracheal tufts. BMC Biol. 2016 Sep 9/19/2016; 14: 78. PMID: 27643786, PMCID: PMC5027632, PII: 10.1186/s12915-016-0305-y, DOI: 10.1186/s12915-016-0305-y, ISSN: 1741-7007.

Suggs JM, Jones TH, Murphree SC, Hillyer JF. CCAP and FMRFamide-like peptides accelerate the contraction rate of the antennal accessory pulsatile organs (auxiliary hearts) of mosquitoes. J. Exp. Biol [print-electronic]. 2016 Aug 8/1/2016; 219(Pt 15): 2388-95. PMID: 27247317, PII: jeb.141655, DOI: 10.1242/jeb.141655, ISSN: 1477-9145.

Hillyer JF. Insect immunology and hematopoiesis. Dev. Comp. Immunol [print-electronic]. 2016 May; 58: 102-18. PMID: 26695127, PMCID: PMC4775421, PII: S0145-305X(15)30089-6, DOI: 10.1016/j.dci.2015.12.006, ISSN: 1879-0089.

Sigle LT, Hillyer JF. Mosquito hemocytes preferentially aggregate and phagocytose pathogens in the periostial regions of the heart that experience the most hemolymph flow. Dev. Comp. Immunol [print-electronic]. 2016 Feb; 55: 90-101. PMID: 26526332, PII: S0145-305X(15)30062-8, DOI: 10.1016/j.dci.2015.10.018, ISSN: 1879-0089.

Hillyer JF. Integrated Immune and Cardiovascular Function in Pancrustacea: Lessons from the Insects. Integr. Comp. Biol [print-electronic]. 2015 Nov; 55(5): 843-55. PMID: 25898841, PII: icv021, DOI: 10.1093/icb/icv021, ISSN: 1557-7023.

Hillyer JF, Estévez-Lao TY, Mirzai HE. The neurotransmitters serotonin and glutamate accelerate the heart rate of the mosquito Anopheles gambiae. Comp. Biochem. Physiol., Part A Mol. Integr. Physiol [print-electronic]. 2015 Oct; 188: 49-57. PMID: 26099947, PII: S1095-6433(15)00168-3, DOI: 10.1016/j.cbpa.2015.06.015, ISSN: 1531-4332.

Hillyer JF. ACCEPTANCE OF THE 2015 HENRY BALDWIN WARD MEDAL: MY JOURNEY IN PARASITOLOGY, AND WITH PARASITOLOGISTS. J. Parasitol [print-electronic]. 2015 Sep 9/3/2015; PMID: 26335281, DOI: 10.1645/15-871, ISSN: 1937-2345.

Ellison HE, Estévez-Lao TY, Murphree CS, Hillyer JF. Deprivation of both sucrose and water reduces the mosquito heart contraction rate while increasing the expression of nitric oxide synthase. J. Insect Physiol [print-electronic]. 2015 Mar; 74: 1-9. PMID: 25640058, PII: S0022-1910(15)00025-6, DOI: 10.1016/j.jinsphys.2015.01.011, ISSN: 1879-1611.

League GP, Onuh OC, Hillyer JF. Comparative structural and functional analysis of the larval and adult dorsal vessel and its role in hemolymph circulation in the mosquito Anopheles gambiae. J. Exp. Biol [print-electronic]. 2015 Feb 2/1/2015; 218(Pt 3): 370-80. PMID: 25524976, PMCID: PMC4317240, PII: jeb.114942, DOI: 10.1242/jeb.114942, ISSN: 1477-9145.

Kong L, Lu A, Guan J, Yang B, Li M, Hillyer JF, Ramarao N, Söderhäll K, Liu C, Ling E. Thermolysin damages animal life through degradation of plasma proteins enhanced by rapid cleavage of serpins and activation of proteases. Arch. Insect Biochem. Physiol [print-electronic]. 2015 Jan; 88(1): 64-84. PMID: 25042057, DOI: 10.1002/arch.21178, ISSN: 1520-6327.

Boppana S, Hillyer JF. Hemolymph circulation in insect sensory appendages: functional mechanics of antennal accessory pulsatile organs (auxiliary hearts) in the mosquito Anopheles gambiae. J. Exp. Biol [print-electronic]. 2014 Sep 9/1/2014; 217(Pt 17): 3006-14. PMID: 24948635, PII: jeb.106708, DOI: 10.1242/jeb.106708, ISSN: 1477-9145.

Hillyer JF, Strand MR. Mosquito hemocyte-mediated immune responses. Curr Opin Insect Sci. 2014 Sep 9/1/2014; 3: 14-21. PMID: 25309850, PMCID: PMC4190037, DOI: 10.1016/j.cois.2014.07.002, ISSN: 2214-5745.

Raphemot R, Estévez-Lao TY, Rouhier MF, Piermarini PM, Denton JS, Hillyer JF. Molecular and functional characterization of Anopheles gambiae inward rectifier potassium (Kir1) channels: a novel role in egg production. Insect Biochem. Mol. Biol [print-electronic]. 2014 Aug; 51: 10-9. PMID: 24855023, PMCID: PMC4121989, PII: S0965-1748(14)00078-2, DOI: 10.1016/j.ibmb.2014.05.002, ISSN: 1879-0240.

Lu A, Li X, Hillyer JF, Beerntsen BT, Söderhäll K, Ling E. Recombinant Drosophila prophenoloxidase 1 is sequentially cleaved by a-chymotrypsin during in vitro activation. Biochimie [print-electronic]. 2014 Jul; 102: 154-65. PMID: 24657220, PII: S0300-9084(14)00087-X, DOI: 10.1016/j.biochi.2014.03.007, ISSN: 1638-6183.

Hillyer JF, Estévez-Lao TY, de la Parte LE. Myotropic effects of FMRFamide containing peptides on the heart of the mosquito Anopheles gambiae. Gen. Comp. Endocrinol [print-electronic]. 2014 Jun 6/1/2014; 202: 15-25. PMID: 24747482, PII: S0016-6480(14)00125-7, DOI: 10.1016/j.ygcen.2014.03.048, ISSN: 1095-6840.

Estévez-Lao TY, Hillyer JF. Involvement of the Anopheles gambiae Nimrod gene family in mosquito immune responses. Insect Biochem. Mol. Biol [print-electronic]. 2014 Jan; 44: 12-22. PMID: 24200842, PII: S0965-1748(13)00193-8, DOI: 10.1016/j.ibmb.2013.10.008, ISSN: 1879-0240.

Estévez-Lao TY, Boyce DS, Honegger HW, Hillyer JF. Cardioacceleratory function of the neurohormone CCAP in the mosquito Anopheles gambiae. J. Exp. Biol. 2013 Feb 2/15/2013; 216(Pt 4): 601-13. PMID: 23364571, PII: 216/4/601, DOI: 10.1242/jeb.077164, ISSN: 1477-9145.

King JG, Hillyer JF. Spatial and temporal in vivo analysis of circulating and sessile immune cells in mosquitoes: hemocyte mitosis following infection. BMC Biol. 2013; 11: 55. PMID: 23631603, PMCID: PMC3660217, PII: 1741-7007-11-55, DOI: 10.1186/1741-7007-11-55, ISSN: 1741-7007.

Xu J, Hillyer JF, Coulibaly B, Sacko M, Dao A, Niaré O, Riehle MM, Traoré SF, Vernick KD. Wild Anopheles funestus mosquito genotypes are permissive for infection with the rodent malaria parasite, Plasmodium berghei. PLoS ONE [electronic-print]. 2013; 8(4): e61181. PMID: 23593423, PMCID: PMC3620233, PII: PONE-D-12-26612, DOI: 10.1371/journal.pone.0061181, ISSN: 1932-6203.

Chen W, Hillyer JF. FlyNap (triethylamine) increases the heart rate of mosquitoes and eliminates the cardioacceleratory effect of the neuropeptide CCAP. PLoS ONE [electronic-print]. 2013; 8(7): e70414. PMID: 23875027, PMCID: PMC3713048, PII: PONE-D-13-23200, DOI: 10.1371/journal.pone.0070414, ISSN: 1932-6203.

Murdock CC, Paaijmans KP, Bell AS, King JG, Hillyer JF, Read AF, Thomas MB. Complex effects of temperature on mosquito immune function. Proc. Biol. Sci [print-electronic]. 2012 Aug 8/22/2012; 279(1741): 3357-66. PMID: 22593107, PMCID: PMC3385736, PII: rspb.2012.0638, DOI: 10.1098/rspb.2012.0638, ISSN: 1471-2954.

Coggins SA, Estévez-Lao TY, Hillyer JF. Increased survivorship following bacterial infection by the mosquito Aedes aegypti as compared to Anopheles gambiae correlates with increased transcriptional induction of antimicrobial peptides. Dev. Comp. Immunol [print-electronic]. 2012 Jul; 37(3-4): 390-401. PMID: 22326457, PII: S0145-305X(12)00023-7, DOI: 10.1016/j.dci.2012.01.005, ISSN: 1879-0089.

Hillyer JF, Estévez-Lao TY, Funkhouser LJ, Aluoch VA. Anopheles gambiae corazonin: gene structure, expression and effect on mosquito heart physiology. Insect Mol. Biol [print-electronic]. 2012 Jun; 21(3): 343-55. PMID: 22404523, DOI: 10.1111/j.1365-2583.2012.01140.x, ISSN: 1365-2583.

King JG, Hillyer JF. Infection-induced interaction between the mosquito circulatory and immune systems. PLoS Pathog [print-electronic]. 2012; 8(11): e1003058. PMID: 23209421, PMCID: PMC3510235, PII: PPATHOGENS-D-12-02009, DOI: 10.1371/journal.ppat.1003058, ISSN: 1553-7374.

Hillyer JF. Introduction of Bruce M. Christensen, recipient of the 2011 Clark P. Read Mentor Award. J. Parasitol [print-electronic]. 2011 Dec; 97(6): 974-5. PMID: 21671724, DOI: 10.1645/GE-2885.1, ISSN: 1937-2345.

King JG, Vernick KD, Hillyer JF. Members of the salivary gland surface protein (SGS) family are major immunogenic components of mosquito saliva. J. Biol. Chem [print-electronic]. 2011 Nov 11/25/2011; 286(47): 40824-34. PMID: 21965675, PMCID: PMC3220476, PII: M111.280552, DOI: 10.1074/jbc.M111.280552, ISSN: 1083-351X.

Honegger HW, Estévez-Lao TY, Hillyer JF. Bursicon-expressing neurons undergo apoptosis after adult ecdysis in the mosquito Anopheles gambiae. J. Insect Physiol [print-electronic]. 2011 Jul; 57(7): 1017-22. PMID: 21554887, PII: S0022-1910(11)00115-6, DOI: 10.1016/j.jinsphys.2011.04.019, ISSN: 1879-1611.

Glenn JD, King JG, Hillyer JF. Structural mechanics of the mosquito heart and its function in bidirectional hemolymph transport. J. Exp. Biol. 2010 Feb 2/15/2010; 213(4): 541-50. PMID: 20118304, PII: 213/4/541, DOI: 10.1242/jeb.035014, ISSN: 1477-9145.

Hillyer JF, Estévez-Lao TY. Nitric oxide is an essential component of the hemocyte-mediated mosquito immune response against bacteria. Dev. Comp. Immunol [print-electronic]. 2010 Feb; 34(2): 141-9. PMID: 19733588, PII: S0145-305X(09)00192-X, DOI: 10.1016/j.dci.2009.08.014, ISSN: 1879-0089.

Aliota MT, Fuchs JF, Rocheleau TA, Clark AK, Hillyer JF, Chen CC, Christensen BM. Mosquito transcriptome profiles and filarial worm susceptibility in Armigeres subalbatus. PLoS Negl Trop Dis. 2010; 4(4): e666. PMID: 20421927, PMCID: PMC2857672, DOI: 10.1371/journal.pntd.0000666, ISSN: 1935-2735.

Andereck JW, King JG, Hillyer JF. Contraction of the ventral abdomen potentiates extracardiac retrograde hemolymph propulsion in the mosquito hemocoel. PLoS ONE. 2010; 5(9): e12943. PMID: 20886066, PMCID: PMC2944847, DOI: 10.1371/journal.pone.0012943, ISSN: 1932-6203.

Hillyer JF. Mosquito immunity. Adv. Exp. Med. Biol. 2010; 708: 218-38. PMID: 21528701, ISSN: 0065-2598.

Hillyer JF. Transcription in mosquito hemocytes in response to pathogen exposure. J. Biol [print-electronic]. 2009; 8(5): 51. PMID: 19519953, PMCID: PMC2736665, PII: jbiol151, DOI: 10.1186/jbiol151, ISSN: 1475-4924.

Hillyer JF, Barreau C, Vernick KD. Efficiency of salivary gland invasion by malaria sporozoites is controlled by rapid sporozoite destruction in the mosquito haemocoel. Int. J. Parasitol [print-electronic]. 2007 May; 37(6): 673-81. PMID: 17275826, PMCID: PMC1905829, PII: S0020-7519(06)00440-1, DOI: 10.1016/j.ijpara.2006.12.007, ISSN: 0020-7519.

Hillyer JF, Christensen BM. Mosquito phenoloxidase and defensin colocalize in melanization innate immune responses. J. Histochem. Cytochem. 2005 Jun; 53(6): 689-98. PMID: 15928318, PII: 53/6/689, DOI: 10.1369/jhc.4A6564.2005, ISSN: 0022-1554.

Wang X, Fuchs JF, Infanger LC, Rocheleau TA, Hillyer JF, Chen CC, Christensen BM. Mosquito innate immunity: involvement of beta 1,3-glucan recognition protein in melanotic encapsulation immune responses in Armigeres subalbatus. Mol. Biochem. Parasitol. 2005 Jan; 139(1): 65-73. PMID: 15610820, PII: S0166-6851(04)00274-9, DOI: 10.1016/j.molbiopara.2004.09.009, ISSN: 0166-6851.

Hillyer JF, Schmidt SL, Fuchs JF, Boyle JP, Christensen BM. Age-associated mortality in immune challenged mosquitoes (Aedes aegypti) correlates with a decrease in haemocyte numbers. Cell. Microbiol. 2005 Jan; 7(1): 39-51. PMID: 15617522, PII: CMI430, DOI: 10.1111/j.1462-5822.2004.00430.x, ISSN: 1462-5814.

Wang X, Rocheleau TA, Fuchs JF, Hillyer JF, Chen CC, Christensen BM. A novel lectin with a fibrinogen-like domain and its potential involvement in the innate immune response of Armigeres subalbatus against bacteria. Insect Mol. Biol. 2004 Jun; 13(3): 273-82. PMID: 15157228, PII: IMB484, DOI: 10.1111/j.0962-1075.2004.00484.x, ISSN: 0962-1075.

Hillyer JF, Schmidt SL, Christensen BM. The antibacterial innate immune response by the mosquito Aedes aegypti is mediated by hemocytes and independent of Gram type and pathogenicity. Microbes Infect. 2004 Apr; 6(5): 448-59. PMID: 15109959, PII: S1286457904000425, DOI: 10.1016/j.micinf.2004.01.005, ISSN: 1286-4579.

Boyle JP, Hillyer JF, Yoshino TP. Pharmacological and autoradiographical characterization of serotonin transporter-like activity in sporocysts of the human blood fluke, Schistosoma mansoni. J. Comp. Physiol. A Neuroethol. Sens. Neural. Behav. Physiol [print-electronic]. 2003 Aug; 189(8): 631-41. PMID: 12861423, DOI: 10.1007/s00359-003-0429-8, ISSN: 0340-7594.

Hillyer JF, Schmidt SL, Christensen BM. Hemocyte-mediated phagocytosis and melanization in the mosquito Armigeres subalbatus following immune challenge by bacteria. Cell Tissue Res [print-electronic]. 2003 Jul; 313(1): 117-27. PMID: 12838409, DOI: 10.1007/s00441-003-0744-y, ISSN: 0302-766X.

Johnson JK, Rocheleau TA, Hillyer JF, Chen CC, Li J, Christensen BM. A potential role for phenylalanine hydroxylase in mosquito immune responses. Insect Biochem. Mol. Biol. 2003 Mar; 33(3): 345-54. PMID: 12609519, PII: S0965174802002576, ISSN: 0965-1748.

Hillyer JF, Schmidt SL, Christensen BM. Rapid phagocytosis and melanization of bacteria and Plasmodium sporozoites by hemocytes of the mosquito Aedes aegypti. J. Parasitol. 2003 Feb; 89(1): 62-9. PMID: 12659304, DOI: 10.1645/0022-3395(2003)089[0062:RPAMOB]2.0.CO;2, ISSN: 0022-3395.

Hillyer JF, Christensen BM. Characterization of hemocytes from the yellow fever mosquito, Aedes aegypti. Histochem. Cell Biol [print-electronic]. 2002 May; 117(5): 431-40. PMID: 12029490, DOI: 10.1007/s00418-002-0408-0, ISSN: 0948-6143.

Hillyer JF, Albrecht RM. Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles. J Pharm Sci. 2001 Dec; 90(12): 1927-36. PMID: 11745751, PII: 10.1002/jps.1143, ISSN: 0022-3549.

Smartt CT, Kiley LM, Hillyer JF, Dasgupta R, Christensen BM. Aedes aegypti glutamine synthetase: expression and gene structure. Gene. 2001 Aug 8/22/2001; 274(1-2): 35-45. PMID: 11674996, PII: S0378111901006187, ISSN: 0378-1119.

Zhao X, Smartt CT, Hillyer JF, Christensen BM. A novel member of the RING-finger gene family associated with reproductive tissues of the mosquito, Aaedes aegypti. Insect Mol. Biol. 2000 Jun; 9(3): 301-8. PMID: 10886414, PII: imb189, ISSN: 0962-1075.

Hillyer JF, Albrecht RM. Correlative Instrumental Neutron Activation Analysis, Light Microscopy, Transmission Electron Microscopy, and X-ray Microanalysis for Qualitative and Quantitative Detection of Colloidal Gold Spheres in Biological Specimens. Microsc. Microanal. 1998 Sep; 4(5): 481-90. PMID: 9990870, PII: MIMI98-056K, ISSN: 1435-8115.