Trypanosoma cruzi (T. cruzi) is a parasite which causes Chagas disease. The focus of my research includes molecular biology of the parasite, pathogenesis of Chagas disease and the genetic techniques in this organism. My laboratory studies protein kinases and kinase signaling pathways in T. cruzi, identifying and characterizing components in cAMP-dependent protein kinase (PKA) and mitogen activated protein kinase pathways in T. cruzi. The knowledge can be used for drug development. My group has also advanced molecular genetics in T. cruzi by designing a modified pTREX vector which uses an N-terminal fusion of a ligand-controlled destabilization domain (ddFKBP) to a gene/protein of interest. This vector system allows rapid and reversible protein expression and efficient functional analysis of proteins in different T. cruzi life cycle stages. In addition, my group is creating transgenic T. cruzi for the study of disease mechanism and for vaccine strains. The inducible suicide vector systems in T. cruzi have been established using the degradation domain based on the Escherichia coli dihydrofolate reductase (ecDHFR) linked with toxic or detrimental proteins. These vector systems can be introduced into this organism to create attenuated live parasites which can be induced to undergo a self-destruction process. Using the transgenic T. cruzi strains which induce strong protection against re-infection in mice, effective immunity against T. cruzi infection is being investigated. Infection with T. cruzi is lifelong. A drug that can modulate immune responses and reduce parasite burden will be ideal to use in patients with Chagas disease. As the activity of resolvins is immunoresolvent but not immunosuppressive, we determined if they could have such a therapeutic effect. For that purpose, we tested the consequences of treatment with resolvin D1 in a murine model of T. cruzi infection. The treatment significantly improves the mice infected with T. cruzi. We have recently published an article describing the benefits of resolvin D1 treatment for mice infected with T. cruzi. 

Bao Y, Weiss LM, Braunstein VL, Huang, H. (2008) The role of protein kinase A in Trypanosoma cruzi . Infection and Immunity 76:4757-63(Spotlighted)

Bao Y, Weiss LM, Hashimoto M, Nara T, and Huang H (2009) Protein kinase A regulatory subunit interacts with P- type ATPases in Trypanosoma cruzi Am J Trop Med Hyg. 80(6):941-3.

Bao Y, Weiss LM, Ma YF, Kahn S, and Huang H.(2010) Protein kinase A catalytic subunit interacts and phosphorylates members of trans-sialidase super-family in Trypanosoma cruzi. Microbes and Infection 202(7):1104-13.

Bao Y, Weiss LM , Ma YF, Lisanti MP, Tanowitz HB, Das BC, Zheng R and Huang H.(2010) Molecular cloning and characterization of Mitogen-activated protein kinase 2 in Trypanosoma cruzi. Cell Cycle 2010 Jul 15;9(14):2888-96. Epub 2010 Jul 13.

Huang H (2011) Signal transduction in Trypanosoma cruzi (review) Advance in Parasitology. 2011; 75:325-44.

Taylor MC, Huang H, Kelly JM (2011) Genetic Techniques in Trypanosoma cruzi (review) Advance In Parasitology, 75:231-50.

Ma YF, Weiss LM, Huang H (2012). A method for rapid regulation of protein expression in Trypanosoma cruzi. Int J Parasitol. 42:33-37.

Ma YF, Weiss LM, Huang H (2015). Inducible suicide vector systems for Trypanosoma cruzi.  Microbes and Infection 17: 440-450.

Ma YF, Weiss LM, Huang H (2016). Strategy for the development of vaccines against Chagas disease.  HSOA Journal of Vaccine Research and Vaccination 1:001.

Podešvová L, Huang H, Yurchenko V(2017). Inducible protein stabilization system in  Leishmania mexicana. Mol Biochem Parasitol. 214:62-64

Horta AL, Williams T, Han B, Ma Y, Menezes APJ, Tu V, Talvani A, Weiss LM, Huang H(2020). Resolvin D1 Administration is Beneficial in Trypanosoma cruzi Infection.  Infect Immun.  88(6):e00052-20.  PMID: 32152197.

Williams T, Guerrero-Ros I, Ma Y, Matos Dos Santos F, Scherer PE, Gordillo R, Horta A, Macian F, Weiss LM, Huang H (2020). Induction of effective immunity against Trypanosoma cruzi. Infect Immun. 88(4):e00908-19, PMID: 31907197.

Horta A, Gigley J, Botet M, Lavau G, Weiss LM, Huang H (2024). Memory-like NK cells are a critical component of vaccine to induced immunity to Trypanosoma cruzi infection. J immunol 15: 617-631.