Dr. Harald Surowy

Dr. Harald Surowy

Dr. Harald Surowy

Phone:

+49 6221 42 1461

Building:

Im Neuenheimer Feld 581

Room:

4.105

Projects:

Identification of New Risk Genes for Familial Breast Cancer

To date, still about two thirds of those breast cancer cases with a high-risk familial background cannot be explained by the presence of mutations in high-penetrance breast cancer susceptibility genes such as BRCA1 and BRCA2 or in the further known intermediate to low breast cancer risk genes. Gene-centered approaches and genome-wide association studies to identify the missing majority of genes or genomic loci responsible for breast cancer risk did not attain the sought success. Therefore it is most probable that rare and heterogeneous mutations in gene coding regions throughout the genome are causative for high-risk familial breast cancer. We apply Whole Exome Sequencing to identify such mutations. We conduct large case-control genotyping studies to validate and further elucidate the role of the identified mutations in breast cancer to enable future usages in the estimation of individual cancer risk, disease prevention or in cancer treatment. Additional studies focus on the functional relevance of the identified genes and the associated pathways, as well as the impact of the mutations on the gene functions.

Biomarkers for early detection and prognosis of breast cancer

Despite current efforts concerning the development of treatment strategies or therapeutic agents against cancer, the early recognition of the presence of a tumor is crucial and often the most important factor to increase survival rates. The same holds true for the early recognition of metastasis. Present screening methods do however lack the ability to detect cancer at its earliest stages. As an example, familial high-risk breast cancer patients do often develop high-grade tumors with an unfavorable prognosis despite regular screening efforts. Our aim is to identify molecular biomarkers which allow an accurate and sensitive detection of the early stages in the development of breast and other cancers, long before a tumor can be diagnosed by the current imaging technologies. In addition we seek biomarkers that could enable ore improve the stratification of tumor properties towards an individualized prognosis and subsequent cancer treatment. Our focus is on genetic and epigenetic biomarkers that can be detected in blood samples and can thus be obtained repeatedly and by noninvasive means, which is a major advantage compared to tissue samples. An example is the cell-free circulating DNA in blood plasma, which we currently investigate concerning its origin, integrity and methylation status in different cohorts of cancer patients.

Nucleic acid library generation from low and fragmented/short input amounts

Currently the utility of high-throughput nucleic acid sequencing in the field of epidemiology is very limited. As a major obstacle the current protocols to generate the required nucleic acid fragment libraries require large amounts of input materials. Such amounts cannot routinely be obtained from repeatedly accessible and noninvasive clinical specimen, especially concerning body fluids or blood plasma, however this would be required for large-scale epidemiological studies and screening efforts. The current technologies to create nucleic acid fragment libraries do also not perform well on very short or fragmented nucleic acids, which do however dominate in such samples. Moreover, the current costs to create such fragment libraries are too high to enable the utilization in an epidemiological or screening scale with at least thousands of individuals. To overcome this issue, we have focused on the creation of protocols that can efficiently capture very small amounts of also highly fragmented or short nucleic acids and produce ready-to-sequence fragment libraries in a time- and cost-efficient manner. Recently, we have succeeded in establishing a fundamentally new way of nucleic acid fragment library generation, called Capture and Amplification by Tailing and Switching (CATS). We intensively test and evolve this technique to enable any kind of genomic, transcriptomic or epigenomic sequencing as well as approaches that are centered on panels of specific target genes.

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