Drew Baughman, M.A.

Accessing the Microbial Rare Biosphere via Ultra-High Throughput Metagenomics   abstract

Advisor: James Russo

Nicole M. Bullock, M.A.

Multiple Sclerosis and its Treatment and Drug Development: Past, Present, and Future   abstract

Advisor: Ron Guido

Neelay A. Desai, M.A.

Synthetic Biology:  A Survey and a Discussion of Potential Applications to the Biofuels Industry  abstract

Advisor: Farren Isaacs

Christine Du, M.A.

Alzheimer’s Disease Treatment - Past, Present and Future   abstract

Advisor: Tae-Wan Kim

Eliana Grosser, M.A.

The Prooxidant Activities of Nutraceuticals and Their Effects on Cancer Cells   abstract

Advisor: Harvey Babich

Tommie S. Hata, M.A.

Biotechnology in the High School Classroom   abstract

Advisor: Raymomd Schuch

Mark L. Jacobson, M.A.

Rebooting Stem Cell Science: Embryonic Stem Cells, Induced Pluripotent Stem Cells, and a Path to the Clinic   abstract

Advisor: Daniel Kalderon

Scott A. Kera, M.A.

The Past, Present and Future Directions of Male Pattern Baldness   abstract

Advisor: Ady Athanikar

Danhee Kim, M.A.

Mucopolysaccharidosis Type I: a clinical review and potential alternative approaches for treatment   abstract

Advisor: Maryam Banikazemi

Phillip J. Lee, M.A.

Patenting Human Genes: A Closer Look Into Examining the Question Finally Asked   abstract

Advisor: Allan Morrison

Andrew Lounsberry, M.A.

Biotechnology in DNA Forensics   abstract

Advisor: Howard J. Baum

Latt S. Mansor, M.A.

Exercise as Intervention Against Sarcopenia   abstract

Advisor: Carol E. Garber

Katherine Myers, M.A.

Protein aggregation in a human neuronal model of Huntington’s disease   abstract

Advisor: Ai Yamamoto

Jenna R. Rimberg, M.A.

Ataxia Telangiectasia: Disease Mechanisms & Implications for Therapeutic Discovery  abstract

Advisor: Ron Guido

Shlomit F. Schwalb, M.A.

Diabetes and its Effect on Wound Healing   abstract

Advisor: Evan Mintzer

Kaben Schwartz, M.A.

Modeling Parkinson’s disease In Drosophila melanogaster   abstract

Advisor: Brian McCabe

Seong H. Song, M.A.

Advisor: Sahng Gyoon Kim

Nadia Sookdeo, M.A.

Methods for Improving Ovarian Follicle Viability and Maturation to Preserve Fertility for Cancer Survivors   abstract

Advisor: Ralf C. Zimmerman

Ben Yi Tew, M.A.

CLC Channels and Transporters: Structure-Function Relationships   abstract

Advisor: Arthur Karlin

Thao Tran, M.A. 

The HER Family Receptors in Cancer, Emerging Targets and New Therapeutic Potential   abstract

Advisor: Carol Prives

John C. Tsao, M.A.

The Structural Basis of Protein Design   abstract

Advisor: Wayne A. Hendrickson

Joel Veiga, M.A.

Stochasticity in gene expression and cell fate   abstract

Advisor: Ofer Feinerman

Ashley A. Wentworth, M.A.

Oncology Biomarkers Can Indicate Prognosis and Predict Response to Therapy  abstract

Advisor: Teresa DeLuca

Evera Sze-wah Wong, M.A.

Functional Assessment of Cryopreserved Cells for Automated Patch-clamp  abstract

Advisor: Jian Yang

Muhammad S. Zahari, M.A. 

MicroRNAs and their Roles in Cancer Metastasis   abstract

Advisor: James Russo

Accessing the Microbial Rare Biosphere via Ultra-High Throughput Metagenomics

Drew Baughman, M.A. 2010

Metagenomic approaches, combined with ultra-high throughput sequencing, can be used to investigate phylotype richness and evenness in microbial communities. Particularly, 16S rRNA surveys in concert with next generation sequencing (NGS) platforms, can access the rare biosphere- those extremely diverse taxa comprising less than .01% of local microbial diversity. This review introduces an apparently ubiquitous feature of local prokaryotic biodiversity, and its potential ecological importance as suggested by the 'seed bank' hypothesis, which proposes that the rare biosphere functions as an innate genetic reservoir capable of dynamic functional versatility following environmental disruptions. Additionally, the vagaries of microbial species phylogeny, potential sources of methodological bias, and a summary of performance considerations for next and third generation sequencing platforms that may be employed in the endeavor, are also considered. The enhanced throughput of NGS enables more representative sampling of these enormous and phylotypically diverse memberships, generating data that not only illuminates principles of microbial ecology, but also is fundamental to understanding essential ecological processes, such as speciation, extinction and migration.

Multiple Sclerosis and its Treatment and Drug Development: Past, Present, and Future

Nicole M. Bullock, M.A. 2010

Multiple sclerosis is a disease of the central nervous system in which the immune system attacks the myelin sheaths around the brain and spinal cord.  This leads to scarring and demyelination resulting in symptoms like the loss of visions, balance, coordination, etc.  There are approximately 400,000 Americans that have been diagnosed with multiple sclerosis and 2.5 million people worldwide.  Although the specific mechanism in multiple sclerosis that triggers an attack by the immune system remains unknown, there are several FDA approved medications that slow down the underlying course of multiple sclerosis. Knowledge and treatment of the disease could not advance without a deeper understanding of biology and the related advancements in biotechnology.

Synthetic Biology: A Survey and a Discussion of Potential Applications to the Biofuels Industry

Neelay A. Desai, M.A. 2010

The emerging field of synthetic biology is allowing scientists to move from manipulating individual genes to altering biochemical pathways and even entire genomes.  Synthetic biologists are bringing an “engineering mindset” to biology by designing and creating artificial gene networks to better understand and respond to the complexity of nature.  Additionally, synthetic gene synthesis has allowed the design and transplantation of entire genomes.  Scientists are now using artificial genomes to derive the “minimal cell,” which is a cell with only the minimum amount of DNA required to survive, i.e. with all other “extraneous” DNA removed.  Some speculate that this “minimal cell” could be used as a generic “chassis” for future genetic engineering applications.  Biofuel production is receiving a great deal of attention from synthetic biologists.  The search is on to engineer either an existing, well-characterized organism to produce biofuels or to engineer an organism that naturally produces fuel for industrial suitability.  Several leading companies are exploring each approach.  The field of synthetic biology appears to be on the cusp of major advances, and it has the potential to change life as we know it.

Alzheimer’s Disease Treatment - Past, Present and Future 

Christine Du, M.A. 2010

It has been one hundred years since the discovery of Alzheimer’s disease (AD), yet this neuropathological condition continues to affect 5.2 million of people in the U.S. and 26 million people worldwide; the situation continues to worsen. The current standard of care involves cholinesterase inhibitors and NMDA receptor antagonists, both of which offer only minor symptomatic relief. To date, there exists no FDA-approved disease modifying drugs for AD. Fortunately, in the past decade a number of major advances have been made in our understanding regarding to etiology and molecular basis of the disease. Novel pathways and molecular targets that contribute to AD have been discovered and led ways for researchers to target various root causes of this devastating disease in the hopes to develop mechanism-based therapeutics for AD. This paper discusses our current understanding on genetic and pathological changes in the brain that leads to AD pathogenesis and how such discoveries translate into the development of new therapeutic strategies and subsequent clinical and preclinical trials for AD treatments in the 21st century. The paper will also provide introduction and in-depth evaluation of the major clinical trials for AD therapeutics, with emphasis on agents that target β-amyloid and tau metabolism, including γ-secretase inhibition, γ-secretase inhibition and modulation, Aβ vaccine and other immunotherapies, non-steroidal anti-inflammatory drugs (NSAIDs) and statins. Moreover, the paper will discuss several emerging therapeutic approaches at early stage based on major preclinical discoveries on new therapeutic targets of AD. This steady influx of novel and unconventional therapeutic approaches provides good reasons for optimism in the face of AD. 

The Prooxidant Activities of Nutraceuticals and Their Effects on Cancer Cells

Eliana Grosser, M.A. 2010

Polyphenolic nutraceuticals have been promoted primarily as antioxidants, able to interact with reactive oxygen species, thereby preventing cellular damage that could possibly lead to transformation of normal cells to cancer cells.  Current research, conducted with in vitro cell cultures, shows these polyphenolic nutraceuticals also have prooxidant capabilities, which may be the underlying mechanism for some of their anticancerous effects.

Many different cell culture protocols have been used to ascertain the deleterious effects of the prooxidant nature of polyphenols to cancer cells. Some studies used scavengers of reactive oxygen species, e.g., divalent cobalt, pyruvate, catalase, and endogenous antioxidants, e.g., N-acetyl-L-cysteine, to detoxify polyphenols added to cells in culture. Others, demonstrated the depletion of intracellular reduced glutathione, a tripeptide and the cell’s main defense against oxidative stress, upon exposure of cells to polyphenols. Still other research compared the relative sensitivities of cancer cells and normal cells to common polyphenols and showed the greater sensitivity of cancer, than of normal, cells. Such research may be suitable to develop new chemotherapeutic drug regimens that incorporate the consumption of nutraceutical polyphenols that are selectively toxic towards cancer cells, thereby minimizing the adverse side effects on the normal cells.

In vitro studies are not entirely reflective of the response of the whole organism, whether a laboratory animal or a human being, as in vitro conditions do not imitate the in vivo situation. Animal models have been used to evaluate the effects of polyphenols on a whole organism, however, their focus has been on the antioxidant property of nutraceuticals polyphenols; less is known on the response of humans. These latter studies are important, as the concentration of the polyphenol ingested is much different from the concentration actually reaching the target cells. These differences need to be determined before polyphenol nutraceuticals can be used in future cancer therapies.

Biotechnology in the High School Classroom

Tommie S. Hata, M.A. 2010

This is a practical lab reference and manual for both the experienced high school teacher who is already incorporating biotechnology activities in the classroom and for the teacher who is just starting to do so. This manual shares tips and methods to make biotechnology activities more accessible in the classroom environment. The recommendations and protocols are based on experience in both the research laboratory and the high school classroom.

“What considerations should I make when setting up a teaching laboratory at my school?” “How do I break up a miniprep protocol that can’t be complete in a single class period?” “What is a good way to make antibiotic solutions and enzymes readily accessible to students throughout the semester?” This manual answers these questions and many more.

This manual will help teachers to move beyond using “kits” from big vendors and to develop your own activities.Itwill help to determine where to get the necessary reagents and how to organize these resources in the classroom for students. Along with the motivation of an innovative and resourceful teacher, this manual will help incorporate more biotechnology activities into the high school science curriculum.

Rebooting Stem Cell Science: Embryonic Stem Cells, Induced Pluripotent Stem Cells, and a Path to the Clinic

Mark L. Jacobson, M.A. 2010

Stem cells may one day be used to treat, and even cure, a wide variety of diseases and injuries from acute tissue damage, to blindness, to Lou Gehrig's disease. By manipulating the fate of these progenitor cells, researchers and clinicians hope to generate specific types of cells or tissue that can be used to replace damaged or diseased tissue according to a patient's needs. Unfortunately, progress towards achieving this goal has been slow. Stem cell science is complex and the field has been weighed down significantly by ethical concerns, funding limitations, and political acts. Progress is being made, however, towards the development of viable therapeutics. An advancement that has proven particularly promising is the development of a novel method to generate stem cells by converting adult somatic cells into an embryonic-like state. Known as induced pluripotent stem cells (iPS cells), the cells are not derived from human embryos so they alleviate many of the significant ethical concerns and political barriers to the use of stem cells in the lab and clinic. Many laboratories are exploring techniques to generate these cells with therapeutically suitable methods. In addition to transplantation therapy, other downstream applications of iPS cells are being investigated such as novel developmental and disease models and as drug discovery tools. Owing to the youth of the field, much remains to be accomplished before iPS cells may be brought to the clinic and then receive regulatory approval for marketing. This review presents a history of the field and seeks to identify key obstacles and milestones towards the development of iPS cell-based therapies and offers strategies to overcome them.

Rebooting Stem Cell Science: Embryonic Stem Cells, Induced Pluripotent Stem Cells, and a Path to the Clinic

Scott A. Kera, M.A. 2010

Stem cells may one day be used to treat, and even cure, a wide variety of diseases and injuries from acute tissue damage, to blindness, to Lou Gehrig's disease. By manipulating the fate of these progenitor cells, researchers and clinicians hope to generate specific types of cells or tissue that can be used to replace damaged or diseased tissue according to a patient's needs. Unfortunately, progress towards achieving this goal has been slow. Stem cell science is complex and the field has been weighed down significantly by ethical concerns, funding limitations, and political acts. Progress is being made, however, towards the development of viable therapeutics. An advancement that has proven particularly promising is the development of a novel method to generate stem cells by converting adult somatic cells into an embryonic-like state. Known as induced pluripotent stem cells (iPS cells), the cells are not derived from human embryos so they alleviate many of the significant ethical concerns and political barriers to the use of stem cells in the lab and clinic. Many laboratories are exploring techniques to generate these cells with therapeutically suitable methods. In addition to transplantation therapy, other downstream applications of iPS cells are being investigated such as novel developmental and disease models and as drug discovery tools. Owing to the youth of the field, much remains to be accomplished before iPS cells may be brought to the clinic and then receive regulatory approval for marketing. This review presents a history of the field and seeks to identify key obstacles and milestones towards the development of iPS cell-based therapies and offers strategies to overcome them.

Mucopolysaccharidosis Type I: a clinical review and potential alternative approaches for treatment

Danhee Kim, M.A. 2010

Mucopolysaccharidosis I is one of approximately 50 known lysosomal storage disorders caused by the absence or deficiency of the lysosomal enzyme alpha-L-iduronidase. Pathologic accumulation of its substrate, glycoaminoglycans (GAGs) results in devastating clinical manifestations with varying degrees of involvement in skeletal, cardiac, digestive, respiratory, and central nervous system. The disease is usually fatal, with average expected life span of one or, at most, two decades.

To date, no curative treatment is available despite the significant progress and remarkable changes that have been made in the area of lysosomal storage disorders.  Current therapeutics includes only the palliative treatments that lessen the severity of the symptoms in attempts to improve the quality of a patient’s life.

Enzyme replacement therapy is currently the standard-of-care for MPS I yet presents considerable limitations and challenges.  Primary among them is the need to treat neurodegenerative components of MPS I.  Although hematopoietic stem cell transplantation has shown improvements in neurologic symptoms in MPS I patients, the therapy holds risks of morbidity and mortality that cannot be disregarded.  To circumvent some of the limitations of currently available treatment strategies like ERT or HSCT, research and developmental activities have been pursuing a new strategy called small molecule therapy.  A small molecule therapy generally includes an orally-administered pharmacological agent that is designed to produce extremely targeted and selective effect either on the lysosomal enzymatic activity or the production of its substrate, GAG.

In order to fulfill the medical need of MPS patients, the combinatorial effects of the different therapeutic approaches should actively be explored to achieve synergy.  Development of neonatal screening for MPS I is required to promote early diagnosis and intervention of therapies.  Since the disease is highly heterogenous, a proper method to measure the severity of the symptoms or to monitor therapeutic efficacy may further optimize the clinical outcome in MPS patients. 

Patenting Human Genes: A Closer Look Into Examining the Question Finally Asked

Phillip J. Lee, M.A. 2010

Breast cancer susceptibility genes are tumor suppressor genes, the mutant phenotype that predisposes to breast and ovarian cancer.  Patents directed to these human genes have been at the center of controversy in the biotechnology industry, awakening the issue of whether human gene patenting detrimentally affects public health and, ultimately, whether human DNA sequences corresponding to human genes should be patentable.  Specifically, the United States Patent Office has been, for decades, granting patent rights directed to isolated DNA sequences.  As such, patenting isolated DNA sequences was common practice, or at least, the practice has not faced a section 101 scrutiny, whether DNA is patentable subject matter.  The question has been presented to a federal court.  A recent opinion reasoned that DNA sequences provide for basic biological information that cannot be altered.  Thus, even if isolated, DNA is found in nature, and therefore, not patentable.  Professionals and academics have now put forth considerations for and against patenting human genes, and this paper will address where the controversy lies at this time.

Biotechnology in DNA Forensics

Andrew Lounsberry, M.A. 2010

DNA forensics was first developed by Dr. Jeffreys in the mid 1980’s through the use of RFLP analysis. The early method of RFLP eventually gave way to the widespread use of STR markers in forensic cases; however, there are many steps that must first be taken in order for a DNA sample to be ready for STR analysis. Protocols must be followed with regard to sample collection, presumptive/confirmatory testing, DNA extraction, quantitation and amplification. Today, commercially available kits are used for multiplex PCR that not only amplifies, but also labels the 13 CODIS STR markers with different dyes. The labeling allows the information to be analyzed by the ABI Prism, which yields and electropherogram. Computer software ultimately creates the DNA profile from the electropherogram data. The DNA profile can then be uploaded into a DNA database such as CODIS and used to search for matches.

Often times the DNA recovered from a crime scene is less than ideal. Degraded DNA, mixtures, and low copy number DNA can all be issues. However, there are methods that allow these types of samples to yield accurate DNA profiles. DNA profiles are not exclusively useful in forensic cases. DNA profiles are commonly used in paternity tests, immigration disputes, identification of disaster victims and in missing persons cases. DNA forensics has rapidly evolved since first developed by Dr. Jeffreys and will continue to do so in the future as new technology and new science is developed. 

Exercise as Intervention Against Sarcopenia

Latt S. Mansor, M.A. 2010

Sarcopenia is a gradual loss of muscle mass, size, strength and power particularly amongst sedentary older individuals, thus increasing the risk of falling, loss of independence and may be related to loss of functional capacity. The prevalence of sarcopenia increases significantly as older individuals reach the age above 70 years and it proves to have a significant impact not only on the patients but also the economy.

The factors causing sarcopenia are not fully known but inactivity and low Body Mass Index are two major risk factors for older persons to develop sarcopenia. Physical activities of moderate- to high-intensity have been proven to show significant effects in attenuating muscle loss and in many cases, it enhances skeletal muscle mass, strength, power, endurance and intrinsic neuromuscular activation in both older men and women.

Resistance exercise has shown remarkable results in gaining muscle mass especially by recruiting type II muscle fibers and increasing satellite cells to be differentiated and lead to muscle hypertrophy. Alongside resistance training, protein supplementation is extremely important to provide a positive net protein balance in the body to enhance muscle protein accretion. On the other hand, aerobic endurance exercise increases aerobic capacity and muscle endurance while recruiting type I muscle fibers. Besides, endurance training also increases mitochondrial protein content and enzyme activities, leading to less oxidative damage to muscle cells because oxidative damage may also be one of the factors which cause muscle cell death and muscular atrophy.

Although the modality, frequency and intensity of the exercises could be further modified based on ethnic backgrounds, sex, age groups and health conditions, the best recommendation to date is by the Physical Activity Guidelines for Americans based on strong evidence across studies and population.

Protein aggregation in a human neuronal model of Huntington’s disease

Katherine Myers, M.A. 2010

Huntington’s disease is an autosomal dominant neurodegenerative disorder characterized by chorea, cognitive decline and psychiatric symptoms.  To date, several mouse models have been developed which have lent great insight into the molecular pathology of Huntington’s disease, although the precise mechanism of disease and its treatment in affected individuals remain elusive.  The advent of induced pluripotent stem cell technology in recent years, however, has enabled the development of patient-specific disease models of genetic disorders such as Huntington’s disease. Using a simple, reproducible protocol, fibroblasts from a person with Huntington’s disease were dedifferented to a pluripotent state by introduction of four factors: Oct4, Sox2, Klf4 and c-Myc.  These induced pluripotent stem cells were further directed to differentiate into neurospheres which could be regularly passaged in order to produce neurons.  Induced pluripotent stem cell-derived patient-specific neurons specifically display a protein aggregation phenotype, characteristic of the cellular pathology found in both mice and humans, and should provide a relevant model system for future studies.

Ataxia Telangiectasia: Disease Mechanisms & Implications for Therapeutic Discovery

Jenna R. Rimberg, M.A. 2010

Ataxia telangiectasia (AT) is a rare, heritable disease that manifests pleiotropic clinical symptoms early in childhood and lacks a primary cure or preventative treatment. The disease was first classified in 1958 by Boder & Sedgwick as a neurodegenerative familial syndrome with multisystem deficits including progressive cerebellar ataxia, ocular telangiectasias, sinopulmonary infection, immunodeficiency, cancer susceptibility, reproductive sterility, and radiosensitivity. Since the 1995 discovery of ATM (ataxia telangiectasia, mutated), the single defective gene responsible for the heterogeneous AT phenotype, extensive research efforts have probed the complexity of AT pathophysiology through the investigation of diverse ATM signaling networks in healthy cells. As such, ATM has been implicated for its critical role in DNA damage and oxidative stress repair pathways, as well as in the maintenance of cell cycle checkpoints, telomere stability, and T cell receptor and immunoglobulin gene recombination. Given the essential nature of ATM signaling for genomic stability and cellular vitality, the inability to encode functional ATM protein conferred by the disease genotype, explains the devastating clinical manifestations of ataxia telangectasia. Based on a comprehensive review of the AT literature, the foregoing analysis will investigate hallmark features of the disease, ATM signaling pathways, mechanistic correlations between disease genotype, cellular phenotype, and clinical symptoms, and implications for therapeutic discovery.

Diabetes and its Effect on Wound Healing

Shlomit F. Schwalb, M.A. 2010

A wound is described as some kind of disruption that occurs to a part of the body and has an anatomical, structural and functional change from the original area. Wound healing is the process by which the injured area returns to the original condition in which the area appeared and functioned as previously. Wound healing is achieved through four different stages, which are hemostasis, inflammation, proliferation and tissue remodeling.  Each of the phases must occur in this precise order and is essential for successful wound healing to occur.

Diabetes as a whole is a hormonal disorder in which the pancreas does not produce a proper amount of insulin needed for the body to maintain a proper blood sugar level. Type 2 diabetes, also called diabetes mellitus, is a condition in which insulin can be produced however, either not enough insulin is produced or the cells do not respond to the produced insulin. Diabetes influences the rate of tissue repair by causing harm to different stages of the healing process. A better understanding on how diabetes affects wound healing may lead to new therapeutic development.

Modeling Parkinson’s disease In Drosophila melanogaster

Kaben Schwartz, M.A. 2010

Neurodegenerative diseases are often caused by a gradual loss of specific populations of neurons. The most prevalent movement disorder and the second most prevalent neurodegenerative disorder is Parkinson’s disease (PD).   The vast majority of these cases are sporadic with no known cause, however, a very small percent of these conditions are familial.  Breakthroughs in human molecular genetics led to the discovery of novel pathways responsible for causing familial PD. The identification of genes associated with familial PD conditions facilitated the development of PD animal models.  This paper discusses new insight obtained in the biology of PD, with an emphasis placed on recent advances using Drosophila to model Parkinson’s disease.

Dental Stem Cells and Tissue Engineering: Current Approaches and Future Perspective

Seong H. Song, M.A. 2010

It is quite common that people, especially the people of advanced age, need to replace a tooth due to injury, caries, or many other severe dental problems. Current treatment for tooth replacement is exceptionally dependent on tooth implantation technique using non-biological materials such as metal or ceramic. Since it is not a biological tooth, there are several functionally important parts that are missing such as periodontal ligament and dental pulp. This leads to higher possibility of mechanical failure, bacterial infection, and less sustainability to many different types of stresses. Biological tooth regeneration and repair using tissue engineering techniques with stem cells would certainly avoid these problems and offer great benefits that current implantation technique cannot. Tissue engineering uses different types of stem cells including periodontal ligament stem cells (PDLSC), dental follicle stem cells (DFSC), and dental pulp stem cells (DPSC), just to name a few. It is a promising technique to accomplish whole biological tooth regeneration as well as partial tooth repair. Currently, there are parameters that restrict its application for clinical use. For example, it is difficult to control tooth shape, length of eruption time, and its color. Nonetheless, dental tissue engineering is one of the most extensive and active studies in the field of dentistry and is expected to bring great advantages to well-being of people's oral health.

Methods for Improving Ovarian Follicle Viability and Maturation to Preserve Fertility for Cancer Survivors

Nadia Sookdeo, M.A. 2010

The incidence of cancer in the population continues to rise and treatments such as surgery, chemotherapy, and radiotherapy are beneficial, but not without consequence to the quality of life of survivors. These treatments often lead to a decrease or complete cessation of ovarian function with loss of fertility, and early onset of menopause. Cancer treatments perturb the reservoir of primordial follicles that give rise to mature, fertilizable oocytes during folliculogenesis. As a consequence, the window of fertility is decreased or completely closed for these women. In vitro fertilization followed by cryopreservation of embryos has been the established solution to preserving fertility to date however, this method is not ideal for every woman in every stage of life. This unmet need has promoted the emergence of a new field, Oncofertility, to address the growing concerns of every female of any age with cancer wishing to have their own genetic offspring. The field of Oncofertility explores methods to isolate, cryopreserve, mature, and reimplant follicles as an alternative method to embryo freezing to preserve fertility. The intricacies, progress, challenges, and promise of these methods are discussed here.  

CLC Channels and Transporters: Structure-Function Relationships

Ben Yi Tew, M.A. 2010

CLC chloride channels and transporters have given scientists many surprises ever since their discovery. These homodimeric double-barreled channel proteins are key chloride ion regulators and are present in both prokaryotic and eukaryotic cells. The unique structure of CLC channels underlies unique mechanisms of gating and permeation. Surprisingly, the same core CLC structure can form a passive channel or a coupled transporter of two different ions, with the two types differing in only a few amino acid residues. Recent studies have shown that CLCs are capable of associating with different proteins and small molecules, mostly through their intracellular, C-terminal cystathionine-β-synthase domains. In addition, some CLCs are associated with β-subunits, such as Barttin and Ostm1, which promote expression and stabilization of the CLCs.

CLCs play important roles in human physiology and disease. With nine mammalian homologues, CLCs participate in a wide variety of cellular functions, including muscle contraction, transepithelial salt transport, and lysosomal acidification. The disruption of CLC function is associated with diseases such as renal salt wasting, osteopetrosis, and lysosomal disorders.

The HER Family Receptors in Cancer, Emerging Targets and New Therapeutic Potential 

Thao Tran, M.A. 2010

The human epidermal growth factor receptor (HER) family of tyrosine kinases has been of substantial interest due to its crucial role in the development of cancer when its signaling is deregulated. The inhibition of signaling function of individual members in this family, particularly EGFR and HER2, has advanced the treatment of different human cancers. Current therapies have led to our better understanding of the mechanisms of action as well as mechanisms of resistance, which delineate new challenges to realize the full potential of targeting this pathway. This review outlines our current understanding of HER-signaling pathways, re-evaluates the role of emerging targets and discusses the potential for new approaches to target signaling through this family of receptors.

The Structural Basis of Protein Design

John C. Tsao, M.A. 2010

Protein design is the science of altering or creating protein molecules with desired functions. Research using different elements and concepts has been conducted, including the structural aspect of protein design. More specifically, scientific efforts have mainly been focused on protein structure prediction, scaffold design, modification of existing proteins, and de novo protein design. All these methods have resulted in a tremendous amount of structural information about proteins, some more useful than others. Although there are some common themes in these approaches, each technique is nevertheless different in some way. Through a combination of these various design principles, a more unified, defined, and comprehensive depiction of protein design as a field of scientific inquiry can be obtained and utilized for further research endeavors, development, and application. The successes from protein design research have affected and will continue to affect science, technology, and medicine as well as society and the environment. 

Stochasticity in Gene Expression and Cell Fate

Joel Veiga, M.A. 2010

Living organisms exhibit abundant genetic variations within species and experience drastic environmental fluctuations, yet these factors translate into relatively low phenotypic variability. This suggests that development is strongly independent of genetic and environmental variation. Indeed, cell fate is mostly based on deterministic decisions and development is highly regulated and robust both at transcriptional and posttranscriptional levels.

Another layer of variability derives from stochasticity in gene expression at the single cell level. The notion of robustness in gene networks implies that such randomness in cellular protein concentrations must be confined or suppressed so that cellular integrity and function are not impaired. In a sense, excessive cellular variability can be detrimental to cell survival. However, stochasticity can also be advantageous and has implications in development, namely non-deterministic cell fate, where cellular differentiation is left to chance.
In this review I will discuss the origin and significance of stochasticity in gene expression. I will describe the mechanism by which biological systems are or are not robust to stochastic fluctuations and I will defend its significance in promoting cell diversity.

Oncology Biomarkers Can Indicate Prognosis and Predict Response to Therapy

Ashley A. Wentworth, M.A. 2010

Different patients respond differently to the same medications due to inherent genetic variation. The treatment of cancer can be individualized based on information that is gained through biomarker mutation screening as this information can assist physicians in selecting the most appropriate and promising therapy for a given patient. KRAS and BRAF are two prognostic and predictive biomarkers with the potential to guide chemotherapy choices to help achieve the greatest clinical impact by way of individualized treatment for patients with colorectal cancer. Likewise, the BCR-ABL biomarker observed in chronic myeloid leukemia can deliver insight regarding a patient’s prognosis and the treatments to which they are most likely to respond. Finally, EGFR mutation testing has the potential to identify the non-small cell lung cancer patients who may respond best to anti-EGFR therapy and those who should be treated with an
alternative option. These examples of the application of biomarker testing to the field of oncology reveal the immense potential personalized medicine has to improve the treatment of cancer.

Functional Assessment of Cryopreserved Cells for Automated Patch-clamp

Evera Sze-wah Wong, M.A. 2010

Functional cell-based assays in high-throughput screening (HTS) generate valuable information as these assays provide a physiologically relevant system for not only drug screening but also mechanism of drug action. However, the use of high quality cells for cell-based experiments has been critical in order to achieve robust and reproducible results for HTS. Long term culturing of cell lines creates potential variations such as protein expression and growth cycles thereby rendering it difficult to assure cell consistency during multiple test runs. Moreover, cell culture maintenance could be extremely costly and resource-dependent in a high throughput screening environment. The present study demonstrates the functional assessment of cryopreserved cells, stably expressing the human ether-a go-go (hERG) channel, for in vitro cardiac safety profiling of small molecule compounds. The cell freezing protocol was optimized and both the performance and pharmacological profile of the cryopreserved cells was compared to the cells maintained in continuous culture. Results also indicated that hERG cells frozen in high serum (90% FBS) and low serum (10% FBS) supplemented with 10% DMSO could be as effective as cells in continuous culture.

MicroRNAs and their Roles in Cancer Metastasis

Muhhamad S. Zahari, M.A. 2010

MicroRNAs were discovered in 1993, and although they were initially thought to be a unique feature in C. elegans, they were later found to play essential functions in many organisms, including humans. miRNAs control cell division, differentiation, death and numerous other biological processes, by downregulating gene expression at the post-transcriptional level, either by degrading their target mRNAs or inhibiting the mRNA’s translation. When a miRNA is deregulated, which occurs in various cancer malignancies, the regulation of the genes that they govern would consequently be affected. More recently, it has been discovered that miRNAs play important roles specifically in cancer metastasis either by suppressing or activating it. Although the roles of miRNAs in metastasis have been irrefutably demonstrated, the molecular basis underlying their mechanisms is far from complete. To discover the miRNAs that are involved in metastasis and dissect their molecular pathways, investigators’ experimental approaches include identifying differentially expressed miRNAs in tumor tissues, finding their target mRNAs and experimentally demonstrating their effects on metastasis. This review analyzes the studies of miRNAs that are responsible in metastasis and also their potential use in cancer therapy.