Colleagues: Recently Tenured

ASTRID HAASE, M.D., PH.D., NIDDK

Senior Investigator, RNA Biology Section, Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Education: University of Vienna, Austria (M.D.), University of Basel, Switzerland (Ph.D. in Biochemistry)

Training: Postdoctoral Fellow at the Cold Spring Harbor Laboratory (CSHL) in Cold Spring Harbor, New York (2007—2015); graduate student at Friedrich Miescher Institute for Biomedical Research (FMI) in Basel, Switzerland (2002—2007); undergraduate researcher at the Institute for Molecular Pathology (IMP)in Vienna, Austria (2000—2002)

Came to NIH: In 2015 as a Stadtman Tenure-Track Investigator at NIDDK.

Outside interests: I enjoy spending time with my family, another RNA enthusiast and a creative 6-year-old princess. We love road trips, music, and cooking together.

Website: https://irp.nih.gov/pi/astrid-haase

Research interests: Retroviruses and transposons pose a threat to genome stability. In the ongoing arms race with these mobile genetic elements, host genomes suffer insults, accumulate scars, and in rare instances adopt transposon sequences for their own use. But above all, they establish control. RNA-guided immunity, the CRISPR/Cas method, and RNA interference pathways restrict mobile genetic elements to protect genome integrity.

We study PIWI-interacting RNA (piRNA) that controls transposon activity in animal germ cells to ensure the survival of species. Self-nonself discrimination is at the very core of successful defense and relies on complementary base pairing in RNA-guided immunity. How the millions of piRNA sequences faithfully discriminate self from nonself and adapt to novel genomic invaders remain key outstanding questions in genome biology. Our previous studies revealed mechanisms of piRNA biogenesis (Nat Commun 10(1):8282019; iScience 25(6):104427, 2022) and function (Genome Res 31(11):2058-2068, 2021; Proc Natl Acad Sci U S A 116(23):11111-11112, 2019), and developed novel methods for future research (Nucleic Acids Res 50(15):e90, 2022).

PiRNAs are largely confined to germ cells, but the initial epigenetic restriction they impose is maintained in adult somatic cells. However, age and disease weaken epigenetic maintenance, and unleashed transposons trigger toxicity and drive mutagenesis. Understanding how transposons are controlled has fundamental implications for age-related diseases, cancer biology, and autoimmune disorders, all of which are associated with progressive loss of transposon control. My team strives to elucidate conserved mechanisms of piRNA-guided transposon restriction with the overarching goal to understand how genomes resolve conflict, establish control, and achieve cooption of resident transposons.

BIN ZHU, PH.D., NCI

Senior Investigator, Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI-DCEG)

Education: University of Michigan, Ann Arbor, Michigan (Ph.D. in biostatistics)

Training: Postdoctoral associate in the Department of Statistical Science, Center for Human Genetics, Duke University (Durham, North Carolina)

Came to NIH: In 2012 as a tenure-track investigator in the Biostatistics Branch, NCI-DCEG

Outside interests: Reading; hiking; strength training

Website: https://irp.nih.gov/pi/bin-zhu

Research interests: I lead a research team that integrates statistics and genomics to understand the etiology of mutational signatures and reveal tumor heterogeneity. Our research involves developing statistical methods and tools as well as conducting scientific investigations to extract mutational signatures and identify their etiologies across different study designs and platforms. We also aim to reveal inter- and intratumor heterogeneity, with implications for translation and clinical practice.

Recognizing the importance of understanding the relationship between germline variants and tumor somatic mutations, we were the first to identify an inverse association between common germline risk variants and somatic mutation burden in breast cancer (Br J Cancer 115(6):752-760, 2016). We co-led a pan-cancer, genome-wide association analysis of common germline variants and mutational signatures and identified an APOBEC deletion polymorphism associated with mutational signatures attributed to APOBEC deaminases (Nature 578(7793):82-93, 2020). Although the etiology of the APOBEC signature has been well studied, identifying the underlying causes for many other signatures remains challenging. Therefore, we proposed a semiparametric kernel independence test (SKIT) to improve the power to infer the etiology of new mutational signatures (J Am Stat Assoc 116(536):1648-1661, 2021).

We are also interested in understanding inter- and intratumor heterogeneity to improve cancer diagnosis and treatment. For example, our study on gallbladder cancer (GBC) revealed the existence of intertumor heterogeneity in the GBC tumor microenvironment, suggesting that GBC tumors with immunoreactive microenvironments could be potentially treated by immunotherapy (J Hepatol 74(5):1132-1144, 2021). In addition, we investigated intratumor heterogeneity and subclones of papillary renal-cell carcinoma (pRCC) and found that pRCC generally has much less intratumor heterogeneity in driver-gene mutation and copy-number alteration than clear-cell renal-cell carcinoma. This discovery suggests that one biopsy is likely sufficient for diagnosis and molecular analyses of pRCC (Nat Commun 11(1):3096, 2020).