Ana Maria Salicioni

Ana Maria Salicioni, Ph.D.

Research Assistant Professor

Office phone: 413-577-3315

Lab phone: (413) 545-4050

Fax: (413) 545-6326

Email: asalicioni [at] vasci [dot] umass [dot] edu

Office location: 427S ISB

Mailing address:

661 North Pleasant Street, University of Massachusetts-Amherst, MA 01003

Ph.D.: University of San Luis, Argentina (1993)

Postdoctoral Training: St George’s Hospital Medical School, London, UK;
Fox Chase Cancer Center, Philadelphia, PA

Tssk6, a testis-specific serine kinase, in mouse testis (Li et al., MHR 2011)

Molecular mechanisms responsible for sperm function. Role of testis-specific kinases in male fertility and as targets for contraception

Our research is focused on understanding the cell signaling events conducive to sperm capacitation as well as the mechanism(s) by which the capacitated sperm is then able to induce activation and to trigger development in mammalian eggs, ultimately leading to a successful development of the embryo. As part of this task, we are interested in identifying the molecule(s) involved in these events in male germ cells, among which we count the novel family of testis-specific serine protein kinases (TSSKs). The TSSK protein family belongs to the AMPK kinase branch in the CAMK group, and is composed of six members, TSSK1 through TSSK6; whether Tssk5 has all the domains required to be an active kinase has not yet been determined. Using an array of TSSK specific antibodies, we have investigated the localization of TSSKs in mouse and human sperm and demonstrated that TSSK1, TSSK2, TSSK4 and TSSK6 are present in mature sperm (Li et al., 2011). Our studies have provided further support to previous observations indicating that TSSK family members display a different cellular localization, thus suggesting a non-redundant role for these protein kinases. The restricted expression of TSSKs during differentiation of spermatids in the testis, as well as the importance of phosphorylation in signaling pathways, has lead to the prediction that TSSK(s) have an important role(s) in germ cell differentiation and/or sperm function. This prediction has been recently confirmed by the sterile phenotype of the Tssk6 knock-out mice (Spiridonov et al., 2005, Sosnik et al., 2009)and of the double Tssk1 and Tssk2 KO (Xu et al., 2008; Shang et al., 2010). Despite these new discoveries, the specific function and mode of action of Tssks in male reproduction has yet to be determined.

In order to tackle these questions, our research group has chosen the mouse as an experimental model and is applying several traditional biochemistry and molecular biology techniques. More recently, by using a novel phosphoproteomics approach, and in close collaboration with the Visconti lab, we have pinpointed several proteins that are differentially phosphorylated upon sperm capacitation in mice (Platt et al., 2009). Furthermore, we have developed a method for analyzing sperm proteins by metabolic labeling with [32P]-orthophosphate (Salicioni et al., SSR Annual Meeting, 2008). This method should prove very useful for our ongoing studies on the interplay between kinases and phosphatases in the capacitation-associated signaling events.

The characterization of Tssks and the determination of Tssk inhibitors have the potential to lead to new advancements in male infertility and drug development. Besides our current studies using a mouse model, we are analyzing the role of TSSKs in human sperm physiology, and applying this knowledge to male infertility in humans, in collaboration with the Baystate Medical Center Reproductive Biology Lab.

While the advent of new assisted reproductive technologies, especially intracytoplasmic sperm injection (ICSI), has alleviated the number of cases of untreatable male infertility, the molecular defect(s) that impair sperm function is largely unknown. Thus, our research efforts are directed towards a better understanding of the molecular basis of male infertility and to the identification of molecular defects associated with male infertility that could lead to the development of novel therapeutics. On the other hand, an essential component of preventive health is the ability to control fertility through the use of effective contraception. Identification of germ-specific enzymatic molecules such as the TSSK kinases should prove useful targets for specific inhibition of spermiogenesis that will render the sperm unable to fertilize; specific inhibitors of these enzymes will reversibly block reproduction and therefore constitute ideal candidates for a non-hormonal male contraceptive agent.

Research Funding Sources:

Gustavus and Louise Pfeiffer Research Foundation; Collaborative Biomedical Research Program UMass-Amherst-Baystate Medical Center.

Kambayashi T, Behrens EM, Bachmann MH, Salicioni AM, Baldwin CL, Karimi MA, Lee E.  2014.  Measuring cytotoxicity by bioluminescence imaging outperforms the standard chromium-51 release assay.. PlosOne. 10.1371/journal.pone.0089357
Westmuckett AD, Nguyen EB, Herlea-Pana OM, Alvau A, Salicioni AM, Moore KL.  2014.  Impaired Sperm Maturation in Rnase9 Knockout Mice.. Biol Reprod.
Wertheimer E, Krapf D, Vega-Beltran JL, Sánchez-Cárdenas C, Navarrete F, Haddad D, Escoffier J, Salicioni AM, Levin LR, Buck J et al..  2013.  Compartmentalization of Distinct cAMP Signaling Pathways in Mammalian Sperm.. J Biol Chem.
Salicioni AM, Romano FB, Visconti PE.  2012.  Testis-Specific Kinases in male Fertility and as Targets for Contraception. American Pharmaceutical Review. 15(5)
Porambo JR, Salicioni AM, Visconti PE, Platt MD.  2012.  Sperm phosphoproteomics: historical perspectives and current methodologies.. Expert Rev Proteomics. 9(5):533-48.
Li Y, Sosnik J, Brassard L, Reese M, Spiridonov NA, Bates TC, Johnson GR, Anguita J, Visconti PE, Salicioni AM.  2011.  Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis. Molec Hum Reprod. 17(1):42-56.
Krapf D, Arcelay E, Wertheimer EV, Sanjay A, Pilder SH, Salicioni AM, Visconti PE.  2010.  Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors.. The Journal of biological chemistry. 285(11):7977-85.
O'Brien ED, Salicioni AM, Cabada MO, Arranz SE.  2010.  Vitellogenesis in Bufo arenarum: identification, characterization and immunolocalization of high molecular mass lipovitellin during oogenesis.. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology. 155(3):256-65.
Arcelay E, Salicioni AM, Wertheimer E, Visconti PE.  2008.  Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation.. The International journal of developmental biology. 52(5-6):463-72.
Yoon S-Y, Jellerette T, Salicioni AM, Lee HC, Yoo M-S, Coward K, Parrington J, Grow D, Cibelli JB, Visconti PE et al..  2008.  Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.. The Journal of clinical investigation. 118(11):3671-81.
Wertheimer EV, Salicioni AM, Liu W, Trevino CL, Chavez J, Hernández-González EO, Darszon A, Visconti PE.  2008.  Chloride Is essential for capacitation and for the capacitation-associated increase in tyrosine phosphorylation.. The Journal of biological chemistry. 283(51):35539-50.
Salicioni AM, Platt MD, Wertheimer EV, Arcelay E, Allaire A, Sosnik J, Visconti PE.  2007.  Signalling pathways involved in sperm capacitation.. Society of Reproduction and Fertility supplement. 65:245-59.
Jha KN, Salicioni AM, Arcelay E, Chertihin O, Kumari S, Herr JC, Visconti PE.  2006.  Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation.. Molecular human reproduction. 12(12):781-9.
Salicioni AM, Gaultier A, Brownlee C, Cheezum MK, Gonias SL.  2004.  Low density lipoprotein receptor-related protein-1 promotes beta1 integrin maturation and transport to the cell surface.. The Journal of biological chemistry. 279(11):10005-12.
Gonias SL, Wu L, Salicioni AM.  2004.  Low density lipoprotein receptor-related protein: regulation of the plasma membrane proteome.. Thrombosis and haemostasis. 91(6):1056-64.
Salicioni AM, Mizelle KS, Loukinova E, Mikhailenko I, Strickland DK, Gonias SL.  2002.  The low density lipoprotein receptor-related protein mediates fibronectin catabolism and inhibits fibronectin accumulation on cell surfaces.. The Journal of biological chemistry. 277(18):16160-6.
Ma Z, Thomas KS, Webb DJ, Moravec R, Salicioni AM, Mars WM, Gonias SL.  2002.  Regulation of Rac1 activation by the low density lipoprotein receptor-related protein.. The Journal of cell biology. 159(6):1061-70.
Guerreiro Da Silva ID, Hu YF, Russo IH, Ao X, Salicioni AM, Yang X, Russo J.  2000.  S100P calcium-binding protein overexpression is associated with immortalization of human breast epithelial cells in vitro and early stages of breast cancer development in vivo.. International journal of oncology. 16(2):231-40.
Name Phone Office
Majka , Julie Graduate Student 413-545-4050 465A ISB
Murphy , Quinn Undergraduate Research Assistant 413-545-4050 465A ISB