My research interests are integrative in that they require biochemical, cellular and organismic approaches to solve physiological questions. One current aim is to understand mechanisms by which animals survive severe water stress in nature. For example, anydrobiotic animals can survive the removal of greater than 98% of their tissue water. We are currently exploring the roles that Late Embryogenesis Abundant (LEA) proteins play in the desiccation tolerance of cells. LEA proteins are extremely hydrophilic proteins that are intrinsically unstructured in aqueous solution, but surprisingly, many assume their native conformation during drying. LEA proteins are targeted to multiple cellular locations, including mitochondria, and evidence supports that LEA proteins stabilize vitrified sugar glasses thought to be important in the dried state. Intracellular accumulation is tightly correlated with acquisition of desiccation tolerance, and data support their capacity to stabilize other proteins and membranes during drying, especially in the presence of sugars like trehalose. Such lessons learned from organisms that are naturally desiccation tolerant are being applied to cell stabilization problems in the biomedical field with the goal of desiccating mammalian cells for storage at ambient temperature. The ectopic expression of LEA proteins may be helpful in this regard. Integrating such concepts into protocols for biostabilization may bring us closer to the exciting possibility of engineering mammalian cells and tissues that are more tolerant to long-term storage.
Another research focus of our lab is to identify mechanisms that permit animals to enter, survive and exit states of hypometabolism and dormancy. For animals that enter quiescent states under anoxia, the duration of survival is correlated with the degree of metabolic depression. The length of anoxia tolerance increases by three orders of magnitude when ATP turnover under anoxia is depressed from 30% of aerobic values to 1%. Because conservation of energy is critical for survivorship, we are studying mechanisms for downregulating energetically expensive processes like gene expression (transciptional and translational levels), macromolecular turnover, and ion transport. Diapause is another interesting case of dormancy where environmental change is not a prerequisite for inducing the metabolic arrest in many species, but rather the cellular stasis is developmentally programmed. Examples of diapausing organisms include insects, certain crustacean embryos (e.g., the brine shrimp Artemia franciscana), and embryos of annual killifish. We are evaluating the role of differential gene expression as a control mechanism for such states. A recurring strategy to survive harsh environmental impacts is the reduction in cell proliferation and the inhibition of metabolism, or at least a restructuring of metabolic pathways from oxidative phosphorylation to aerobic glycolysis. Lessons learned from organisms that naturally exhibit cell stasis and desiccation tolerance are improving our biostabilization procedures for mammalian cells.
A final research area to briefly mention is our interest in ontogenetic changes in physiological traits observed for invertebrates. We have focused previously on the ontogeny of osmoregulatory capacities in estuarine shrimp and the timing of diapause in sponge gemmules. The ontogenetic acquisition of hypoxia tolerance is a key issue that deserves more exploration in marine invertebrates inhabiting oxygen limited environments.
Hand, S.C., Menze, M.A., Toner, M., Boswell, L. and D. Moore (2011) Expression of LEA proteins during water stress: Not just for plants any more. Annu. Rev. Physiol. 73: 115–134.
Hand, S.C., Menze, M.A., Borcar, A., Patil, Y., Covi, J.A., Reynolds, J.A., and M. Toner, M. (2011) Metabolic restructuring during energy-limited states: Insights from Artemia franciscana embryos and other animals. J. Insect Physiol. 57(5): 584-594.
Chakraborty, N., Menze, M.A., Malsam, J., Aksan, A., Hand, S.C. and M. Toner (2011) Biostabilization of spin-dried mammalian cells. PLoS ONE 6(9): e24916. doi:10.1371/journal.pone.0024916.
Chakraborty, N., Menze, M., Elmoazzen, H., Halong Vu, H., Yarmush, M.L., Hand, S.C. and M. Toner (2011) Improving desiccation tolerance of Chinese Hamster Ovary Cells using a high-capacity trehalose transporter. Cryobiology (in press).
Menze, M.A., Fortner, G., Nag, S. and S.C. Hand (2010) Mechanisms of apoptosis in Crustacea: What conditions induce versus suppress cell death? Apoptosis 15: 293-312.
Menze, M.A., Chakraborty, N., Clavenna, M., Banerjee, M., Liu, X.-H., Toner, M. and S.C. Hand (2010) Metabolic preconditioning of cells with AICAR-riboside: Improved cryopreservation and cell-type specific impacts on energetics and proliferation. Cryobiology 61: 79-88.
Holman, J.D. and S.C. Hand (2009) Metabolic depression is delayed and mitochondrial impairment averted during prolonged anoxia in the ghost shrimp, Lepidophthalmus louisianensis (Schmitt, 1935). J. Exp. Mar. Biol. Ecol. 376(2): 85-93.
Menze, M.A.,Boswell, L., Toner, M., and S.C. Hand (2009) Occurrence of mitochondria-targeted LEA gene in animals increases organelle resistance to water stress. J. Biol. Chem. 284(16): 10714–10719.
Shumin Li, Senior Research Associate, firstname.lastname@example.org
Apurva Borcar, Ph.D. student, email@example.com
Leaf Boswell, Ph.D. student, firstname.lastname@example.org
Daniel Moore, Ph.D. student, email@example.com
Yuvraj Patil, Ph.D. student, firstname.lastname@example.org
Robert Derenbecker, Undergraduate researcher, email@example.com
Hanna Dobard, Undergraduate researcher, firstname.lastname@example.org
Karolina Ellard, Undergraduate researcher, email@example.com
Suman Nag, Undergraduate researcher, firstname.lastname@example.org