Gustavo Arrizabalaga, PhD

Professor of Pharmacology and Toxicology
and of Microbiology and Immunology

Research Interest

My lab focuses on elucidating the cell signaling mechanisms of growth and host pathogen interaction in the intracellular protozoan parasite Toxoplasma gondii.



Post-doctoral Fellow | Stanford University School of Medicine | Advisor: Dr. John Boothroyd


PhD | Massachusetts Institute of Technology, Cambridge, MA | Advisor: Dr. Ruth Lehmann


B.S. | Chemistry with Biology concentration | Haverford College, Haverford PA | Advisor: Dr. Julio De Paula

Honors and Awards


Chair Elect Division AA, American Society for Microbiology


Excellence in Teaching Award | WWAMI Medical Program | University of Idaho


Commitment to Diversity Faculty Award | WWAMI Medical Program | University of Idaho


Excellence in Teaching Award | WWAMI Medical Program | University of Idaho


R.M. Wade Teaching Excellence Award | University of Idaho

2008 - present

Member, Grant review panel | American Heart Association 

Our main interest is the cellular and molecular biology of the protozoan parasite Toxoplasma gondii. Toxoplasma is an obligate intracellular parasite capable of infecting virtually any nucleated cell from a wide range of mammalian and avian species.  Toxoplasma is one of the most widespread and successful protozoan parasites, and it is thought to infect a third of the world's population.

In immunocompromised individuals such as those with AIDS, leukemia, and lymphoma, and in immunosuppressed transplant recipients, new infections or reactivation of encysted parasites can lead to toxoplasmic encephalitis.  Additionally, in congenital infections, the disease can lead to severe neurological problems or even death of a developing fetus. While there are drugs available to treat the acute stage of the parasite, these are often toxic to the patient and are not effective against the chronic stage of the infection. Thus, there is a need to discover new targets for treatment.

Central to the propagation of Toxoplasma within an infected individual as well as to the ensuing pathogenesis is the completion of its lytic cycle, which consists of attachment to a host cell, active invasion, intracellular replication and egress. This cycle depends on the 

coordinated regulation of the parasite’s motility machinery, physiology, and secretory apparatus as well as on the ability of the parasite to adapt to environmental and physiological changes.  My past research focuses on the signaling events and parasite proteins involved in the process by which the parasite exits its host cell [9-12].  Moreover, following up on observations that ionic homeostasis influences Toxoplasma egress, I have studied the role of ion channels and exchangers in the lytic cycle and stress tolerance of the parasite [9, 13]. Based on my program’s discoveries and observations I have focused my work on two interrelated questions: How does the parasite react and adapt to ion concentration changes, including those induced by anti-parasitic drugs? And how does the parasite regulate its motility as it moves from the inside of a cell to the extracellular environment?  To tackle these questions my research program utilizes a multidisciplinary approach, which combines molecular genetics, cell and molecular biology, and physiology. 

Current work in my research group focuses on:

1. Identifying and characterizing the proteins involved in egress and initiation of motility. Using a series of genetic screens and selections we have discovered that a Calcium Dependent Protein Kinase (CDPK), TgCDPK3 is needed for the parasite to respond to the calcium signals that induce the parasite to rapidly exit its host cell. In addition, using  an  animal  model of Toxoplasmosis  we have determined  that  Tgcdpk3 mutant  parasites  have decreased virulence.

Members of the CDPK family of kinases are of special interest as they are only present in plants and apicomplexan parasites and are absent in mammalian cells. Thus, CDPKs are being focused on as potential drug targets. We are currently identifying the 

targets of TgCDPK3 as well as determining the particular steps during in vivo propagation that require this kinase. 

2. Determining mechanisms of drug resistance in Toxoplasma gondii. Work on the parasite’s response to ion fluxes and other related stresses led us to the discovery of an inducible death pathway, which is dependent on a DNA damage response protein. We have recently discovered that disruption of TgMSH-1, a MutS homolog (MSH) in T. gondii, confers resistance to various anti-parasitic drugs including the ionophores monensin and salinomycin and the anti-malarial atovaquone.  MSHs are critical components of the eukaryotic DNA mismatch repair machinery and can signal cell cycle arrest and apoptosis in response to DNA damaging agents.  Accordingly, mammalian cells lacking certain MSHs are resistant to chemotherapeutic drugs, since the signaling of cell cycle arrest is disrupted.  Similarly, we have observed that monensin causes gene expression changes and disruption of the cell cycle in T. gondii in a TgMHS1-dependent manner.  Thus, by studying the adaptation of the parasite to the ionic stress caused by monensin, we have identified a novel protein in T. gondii that plays a role in an inducible death mechanism. 

Interestingly, unlike previously described MSHs involved in signaling, which localize to the nucleus, TgMSH-1 localizes to the parasite mitochondrion. Our working model predicts that certain drugs affect the mitochondrion of the parasite directly or indirectly. This effect results in the activation of a signaling pathway, which includes 

TgMSH-1 and results in parasite death. Our current focus is on identifying the particular stress that induces the TgMSH-1 dependent death as well as the signaling partners of this novel protein.

Selected Publications

Department of Pharmacology and Toxicology | 635 Barnhill Drive, MS A401 | Indianapolis, IN 46202