There are currently no methodologies that allow for epigenome, genome and transcriptome analysis all in a single cell. In addition, there are currently no methodologies that permit repeating the results of these analyses on the same single cells.
Although multidimensional diffusion/relaxation NMR experiments are widely used in materials sciences and engineering applications, preclinical and clinical MRI applications of these techniques were not feasible. Moreover, higher-field MRI scanners posed another obstacle to translation of this NMR method. Their specific absorption rate (SAR) limits the use of multi-echo or CPMG pulse trains, so that the large amounts of data required by these methods cannot be collected in vivo due to exceedingly long scan times.
Steroid hormones have been implicated to play a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes, or hormones involved in androgen regulatory pathway, reportedly influence risk for developing prostate cancer. Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival.
Researchers at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) developed an MRI-method that is based on the acquisition of multiple pulsed field gradient (m-PFG) rather than single-pulsed field gradient (s-PFG) MRI sequences. In particular, double PFG (dPFG) MRI sequences offer higher sensitivity and greater robustness, as they are more sensitive to the effects of “restriction;” i.e., to water trapped within the axon’s intracellular space, and thus to the diameter of the axons.
Neurites of the central nervous system can be conceptualized as cylindrical pores with finite lengths and radii. In response to physical trauma, axons may assume a “beaded” morphology which alters their ability to conduct electrical impulses, impairing brain function. These microstructural changes are thought to underlie some of the cognitive defects observed in patients with traumatic brain injury (TBI). Current methods for characterizing traumatic brain injury (TBI) cannot provide microstructural detail on the 3-dimensional shape of axonal segments.
The pattern or latency connectome was hypothesized to change in physiological development and disease. For example, in amyotrophic lateral sclerosis (ALS), large diameter axons are damaged selectively – while in autism, small-diameter axons may be over-expressed. These anatomical changes are expected to alter the latency connectome or pattern of delays of information transmission between different gray matter areas involved in salient brain networks.
Mantle cell lymphoma (MCL) is a group of aggressive B-cell lymphomas displaying heterogeneous outcomes after treatment. Some patients have the slowly progressing disease that does not require immediate treatment, while others have a disease that rapidly progresses despite highly aggressive treatment. A number of prognostic tools have been described to determine whether patients have slow or rapidly progressing diseases, including the mantle cell lymphoma International Prognostic Index (MIPI) and biomarkers, such as KI-67.
Ataxia telangiectasia mutated and Rad3 Related (ATR) protein kinase is essential for regulating DNA damage checkpoints during the cell cycle. ATR, is phosphorylated at threonine 1989 site (T1989) in response to DNA damage and ATR activation leads to activation of downstream substrates, signaling cascades and cell cycle arrest. ATR is a potential target for anticancer therapeutics to induce cancer cell death by inhibiting cell cycle arrest pathways in response to chemotherapeutics.
Ultrasound-based cancer screening and biopsy imaging technologies are a clinical need. Ultrasound based biopsy imaging can provide a real-time modality for lower cost that is comparable to, or complimentary to MRI imaging. This technology may enable more accurate, less costly and more accessible cancer screening.
Immunotherapy is a promising method of treating cancer that leverages the immune system to promote tumor rejection. However, certain somatic mutations in cancer cells confer resistance to T cell-mediated cytolysis. To improve the effectiveness of immunotherapies for cancer, there exists a need to prospectively identify patients who are most likely to respond to such therapies.