We are studying how disruption of normal epigenetic regulation of developmental programs leads to tumor initiation and tumor progression. In particular, we are focused on how epigenetic hijacking of developmental transcription factors such as HOX genes leads to malignant transformation of normal stem cells.
In addition, we are studying how these processes work in established sarcoma cells to switch chromatin states allowing cells to adapt to new environments and to stress. Understanding the fundamental biology of epigenetic processes in Ewing sarcoma will lead to new treatment strategies that employ less toxic, tumor-targeted drugs i.
Inhibition of the scaffolding protein menin in Ewing sarcoma leads to metabolic rewiring, with specific loss of serine synthesis pathway SSP gene expression and activity.
This creates a metabolic vulnerability that we hypothesize can be therapeutically exploited. The process of rapid proliferation and tumor expansion exposes tumor cells to multiple sources of internal and external stress. Tumor cells have adapted ways to maintain cellular homeostasis that allow them to survive and thrive under conditions that would destroy less resilient cells. Among the most important of these adaptation mechanisms is metabolic reprogramming.
By rewiring their metabolic pathways, cancer cells are able to maintain redox and amino acid homeostasis and epigenetic stability, while generating the extra energy and biomaterials that are necessary to sustain their growth.
Our current studies of Ewing sarcoma are investigating how serine biosynthesis and amino acid flux contribute to tumor progression. Importantly, these studies have identified critical connections between the epigenome and metabolic reprogramming that we hypothesize are necessary for metastasis.
Her passion to discover new cures for childhood cancer led her back to school, where she completed her PhD in pathology and laboratory medicine at the University of British Columbia. In , Lawlor moved to the University of Michigan, where her lab continued to focus its research on basic and translational studies of pediatric solid tumors, in particular Ewing sarcoma.
While at Michigan, she also dedicated her energies to a second passion — graduate and post-graduate education — serving as director of the Cancer Biology PhD graduate and T32 training programs and as associate director of education and training at the Rogel Cancer Center. She is also a professor of Pediatrics at the University of Washington and adjunct professor in the Department of Laboratory Medicine and Pathology.
The overall goal of her research is to discover and define differences between normal developmental and sarcoma biology that will enable discovery of targeted therapeutics that are less toxic to growing children. There is very compelling evidence that modern diets, and environmental factors are responsible for the remarkably high percentage of malocclusion patterns in our society.
One need only examine population groups who do not share our modern diet and environmental factors to see how little malocclusion exists in contrast.
We understand now that the majority of the modern population has symptoms of malocclusion and dysfunction. It is so prevalent, we mistakenly think it is normal. The result is an unhappy smile with crooked teeth, misaligned jaws and tongues that block airways during sleep due to both jaws being retruded and underdeveloped. An epigenetically driven approach can be used which means firstly any negative functional soft tissue influence is corrected, and then appropriate orthopedic stimulation can be utilized to turn on remodeling potential in adults and actual growth in children.
The result is a positive change in the shape, size and position of both upper and lower jaws moving them as close to full genetic potential as possible. Under Dr. Buck's treatment, jaw development strategies result in your healthiest, happiest smile where everything fits, feels good and looks great. Interested in knowing more? Contact us here to schedule a consultation. Correcting the mis-aligned bite is a potential solution for chronic TMJ problems.
Most TMJ treatment involves the use of some kind of removable oral appliance or splint. These can be very successful in reducing many pain and dysfunction symptoms however there are few clinicians who offer a more permanent second phase correction. Fortunately, Dr. Buck can implement an orthodontic solution for TMJ that can eliminate the need for a splint or appliance which is only a partial cure in most cases.
Buck applies epigenetic science prior to moving teeth with braces stimulating jaw development at a foundational level giving the chance for the body to fully develop underdeveloped jaws. With the jaws fully developed everything fits… all the teeth, the jaws, the tongue.
In this environment, Dr. Buck straightens the teeth with orthodontics, building the balanced, beautiful smile on the solid structure of fully developed jaws.
That is your happiest smile possible! Contact us here to schedule a consultation to find out more. Obstructive Sleep Apnea If there is insufficient volume inside the mouth then the tongue is not provided enough room to stay out of the airway. Added to this is that when the upper jaw is underdeveloped the lower jaw becomes trapped behind the deficient upper jaw and is retruded in such a way that it narrows the airway as well.
With epigenetic driven treatments, Dr. Buck can help to improve the capacity of the airway which is a natural outcome following more face forward orthopedic development of both jaws. This treatment strategy may help reduce sleep breathing problems. Sleep apnea is much more serious than simply snoring.
Obstructing the airway reduces oxygen intake which affects your entire health. Distressed breathing also prevents restful sleep. A person feels these exhausting effects in the short-term, but long-term these factors threaten overall health and wellness.
Sleep apnea is linked to serious health-threatening conditions such as high blood pressure and diabetes. Obstructive Sleep Apnea is caused by multiple factors including a structurally diminished airway as a result of underdeveloped jaw structure. The tongue has insufficient room to stay forward out of the airway during sleep and the lower jaw if retruded creates an narrowing of the functional capacity of the airway.
We often see improved measurements of the airway at the base of the tongue and the nasal cavity after jaw development orthopedics in adults and children. The improved airway may contribute to better and deeper sleep. We were all born beautiful, let us help you to recover your genetic potential for full-face forward beauty and health. Many adults seek our orthodontic treatment to straighten their teeth thanks to available new technologies. Whether you are a teen or an adult, orthodontics will make a significant change to your teeth and structure of your mouth.
The best first step is an Epigenetic consult to make sure your orthodontic treatment is performed on a fully developed jaw. Buck will avoid extractions for braces if at all possible.
With Epigenetic science, your jaws will grow to accommodate all your teeth and fit them straightly in the right places.
By beginning your orthodontic treatment with a consult with Dr. Buck, you will have options for care that are best suited for you and are in harmony with physiology, airway and TMJ health. Long term stability and pain free function are possible. Read More. Buck practices and teaches Neuromuscular Dentistry, a non-invasive method of correcting temporomandibular joint disorder TMD.
This common, chronic, painful condition can have many symptoms, most notably jaw pain, clicking in the jaws, headaches including migraine headaches, neck pain and more. The temporomandibular joint, or the jaw joint, affects bone and soft tissues. So, when that joint is dysfunctional, many areas of the body are affected. If you or someone you know is living with chronic jaw, head or neck pain, a consultation with Dr. Buck might be life changing.
Once diagnosed, Dr. This has led researchers to think of the epigenome less as the language in which the environment commands the genes, and more as a way in which the genes adjust themselves to respond better to an unpredictable environment.
The relationship between them is still being worked out, but for geneticist Adrian Bird of the University of Edinburgh, the role of the environment in shaping the epigenome has been exaggerated. All the aforementioned researchers rue the fact that transgenerational epigenetic inheritance is still what most people think of when they hear the word epigenetics, because the past decade has also seen exciting advances in the field, in terms of the light it has shed on human health and disease.
Different people define epigenetics differently, which is another reason why the field is misunderstood. Some define it as modifications to chromatin, the package that contains DNA inside the nuclei of human cells, while others include modifications to RNA. DNA is modified by the addition of chemical groups. Methylation, when a methyl group is added, is the form of DNA modification that has been studied most, but DNA can also be tagged with hydroxymethyl groups, and proteins in the chromatin complex can be modified too.
Researchers can generate genome-wide maps of DNA methylation and use these to track biological ageing, which as everyone knows is not the same as chronological ageing. The past five years have seen the description of many more tissue-specific epigenetic clocks.
He has already identified what he believes to be an epigenetic signature of neurodegenerative disease. While Bird and others argue that the epigenome is predominantly under genetic control, some researchers are interested in the trace that certain environmental insults leave there.
Smoking, for example, has a clear epigenetic signature. James Flanagan of Imperial College London is among those who are exploiting this aspect of the epigenome to try to understand how lifestyle factors such as smoking, alcohol and obesity shape cancer risk.
Indeed, cancer is the area where there is most excitement in terms of the clinical application of epigenetics. One idea, Flanagan says, is that once informed of their risk a person could make lifestyle adjustments to reduce it.
Drugs that remodel the epigenome have been used therapeutically in those already diagnosed with cancer, though they tend to have bad side-effects because their epigenetic impact is so broad.
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