About

Desmond Ang is an applied economist and associate professor at the Harvard Kennedy School of Government. His research examines the causes and consequences of racial discrimination, with a focus on issues such as police violence, community engagement, racial hate, and the long-term effects of federal oversight under the Voting Rights Act. His work has been published in leading journals including the American Economic Review, American Political Science Review, and Quarterly Journal of Economics. He holds a PhD in economics from the University of California, San Diego, and a B.A. from Dartmouth College. His academic interests encompass social policy, fairness and justice, democracy and governance, gender and race, education, poverty, inequality, and opportunity. As a faculty member, he contributes to courses such as 'Race and Racism in Public Policies, Practices, and Perspectives' and is actively involved in research that explores the impact of police violence on inner-city students and community-law enforcement relations.

Research topics

• Cancer research
• Biology
• Genetics

Selected publications

• Aneuploidy and a deregulated DNA damage response suggest haploinsufficiency in breast tissues of <i>BRCA2</i> mutation carriers

  Science Advances · 2020 · 44 citations

  • Biology
  • Cancer research
  • Genetics

  haploinsufficiency and associated DNA damage precede histologic abnormalities in vivo. Using these hallmarks of cancer predisposition will yield unanticipated opportunities for improved risk assessment and prevention strategies in high-risk patients.

  PublisherOA PDFDOI

• Aneuploidy and deregulated DNA damage response define haploinsufficiency in breast tissues of <i>BRCA2</i> mutation carriers

  bioRxiv (Cold Spring Harbor Laboratory) · 2019-08-08

  preprintOpen access

  Abstract Women harboring heterozygous germline mutations of BRCA2 have a 50-80% risk of developing breast cancer, yet the early pathogenesis of these cancers is poorly understood. We sought to reveal early steps in BRCA2 -associated carcinogenesis through analysis of sorted cell populations from freshly-isolated, non-cancerous breast tissues among a cohort of BRCA2 mutation carriers and matched controls. Single-cell whole-genome sequencing demonstrates that &gt;25% of BRCA2 carrier ( BRCA2 mut/+ ) luminal progenitor (LP) cells exhibit sub-chromosomal copy number variations (CNVs), which are rarely observed in non-carriers. Correspondingly, primary BRCA2 mut/+ breast epithelia exhibit spontaneous and replication stress-induced DNA damage together with attenuated replication checkpoint and apoptotic responses, associated with an age-associated expansion of the LP compartment in human carrier tissues. These phenotypes are not associated with loss of wild-type BRCA2 . Collectively, these findings provide evidence for BRCA2 haploinsufficiency and associated DNA damage in vivo that precede histologic abnormalities. These results provide unanticipated opportunities for new cancer risk assessment and prevention strategies in high-risk patients.

  PublisherOA PDFDOI

• Abstract P4-12-04: Clinical evaluation of multigene testing for hereditary breast and ovarian cancer

  Cancer Research · 2015-05-01

  article

  Abstract Background: Advances in DNA sequencing technology have fueled the development of multigene panels for hereditary cancer testing. While such assays are potentially both practical and affordable for routine clinical genetic testing, there remains uncertainty regarding their proper application and interpretation. Among the unanswered questions are which patients are appropriate candidates for such expanded testing; what is the likelihood that finding deleterious variants will alter risk assessment and management, and what is the prevalence of variants of unknown significance (VUS) that may create uncertainty for providers and anxiety for patients. Methods: 821 patients who met NCCN guidelines for BRCA1/2 testing for hereditary breast/ovarian cancer (HBOC) were prospectively recruited at two major academic medical centers. These patients received traditional BRCA1/2 tests as part of their clinical care and also were later tested for a panel of 29 known cancer risk genes. This panel also re-tested BRCA1/2. Both sequence changes and deletions/duplications were reported, and the panel-testing laboratory was blind to the earlier results. Panel testing results were validated by comparison with the earlier data or by independent testing using established technologies. Family history information was collected directly by genetic counselors. Results: 13.8% of the patients carried BRCA1 or BRCA2 mutations, with &amp;gt;99% concordance between the traditional and panel results for these two genes. 53 (7.6%) of the BRCA1/2-negative patients carried mutations in other cancer risk genes. Some of these findings confer a high risk for breast/ovarian cancer (e.g. TP53), while others (i.e. CHEK2, BRIP1, PALB2, RAD51C, CDKN2A, ATM, and NBN) confer a moderate increase in risk. 10 of these 55 patients were positive for genes involved in Lynch syndrome (MLH1, MSH2, MSH6, and PMS2), although breast and ovarian cancer are not uniformly accepted as part of this syndrome. 40% of these patients were heterozygous carriers of pathogenic variants in MUTYH, which have a less clear impact on breast/ovarian cancer, although this rate (3%) is higher than the expected carrier frequency in this population. About 60% of patients had one or more VUS in the 29 genes. The rate of VUS was highly gene dependent, with ATM, APC, and PTCH1 providing the largest number. A small but significant subset of patients did not have personal or family histories consistent with the classical presentation of their identified mutation. Nevertheless, a majority of the non-BRCA1/2 findings would have prompted consideration of a management change for the tested patient even considering the personal and family cancer history. Conclusions: Multigene panel testing for hereditary cancer risk assessment increased the yield of findings with potential clinical impact for almost 8% of patients. This is consistent with prior data from our laboratory and others. This study, carried out in a uniform clinical practice setting and with data collected directly by health care providers, provides a representative view of the benefit from such testing in an unselected patient population. Citation Format: Leif Ellisen, Allison Kurian, Stephen Lincoln, Andrea Desmond, Meredith Mills, Kristen Shannon, Michelle Gabree, Michael Anderson, Yuya Kobayashi, Federico Monzon, James Ford. Clinical evaluation of multigene testing for hereditary breast and ovarian cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-04.

  PublisherDOI

• Abstract P4-12-07: Technical evaluation of multigene testing for hereditary breast and ovarian cancer

  Cancer Research · 2015-05-01

  article

  Abstract Introduction: Next Generation Sequencing, or NGS technology is gaining acceptance in diagnostic laboratories for multigene panel testing. However questions remain about the sensitivity, specificity and clinical implications of this new technology and the expanded testing it enables. Moreover, questions are raised as to whether new laboratories using these methods, typically without the benefit of large historical proprietary databases, can provide similar assessments of pathogenicity as do the previously established providers. Expanding on our recently published work (Kurian et al., JCO 2014) we considered whether NGS testing in an independent laboratory can replace traditional BRCA1/2 tests in patients indicated for hereditary breast/ovarian cancer testing. Methods: We recruited over 800 patients who were indicated for BRCA1/BRCA2 testing under clinical management guidelines, and collected over 200 additional samples to increase the power of this ongoing study. All were tested using an NGS-based multigene panel which reported both DNA sequence and copy-number alterations for BRCA1/2 and 27 other known cancer risk genes. Traditional genetic testing results using established technologies were also available for comparison. In this report we focus on the results for BRCA1/2 and 27 other known cancer risk genes. Results: Sensitivity was high: 261 alterations (196 pathogenic and 65 others) were reported in the traditional genetic data, and all were detected by NGS when the corresponding test was available. In this set are 141 alterations considered technically challenging for NGS: insertions, deletions, and complex sequence changes, as well as very large (chromosome) and small (single exon) copy number changes. Specificity was also high: all NGS variants for which we sought confirmation using independent methods (n&amp;gt;2000) were confirmed, including 51 alterations not previously reported. Determination of pathogenicity was also highly concordant: in all but 2 cases positive reports agreed, and in these 2 cases data were available in the literature to support pathogenicity, although not at a level which meets recent guidelines from the American College of Medical Genetics (ACMG). It is not clear from the diagnostic reports exactly what evidence supported pathogenicity in the traditional data for these 2 cases. Rates of Variants of Unknown Significance (VUS) in BRCA1/2 were somewhat different: about 7% of cases in the NGS data vs. about 4% of fully tested cases in the traditional data had an uncertain report. The root of this difference is also unclear as details are not provided in the traditional reports. Conclusions: NGS can be a viable replacement for traditional genetic testing for hereditary breast and ovarian cancer. Interpretation concordance is high but fully evaluating the details of this is hampered by the limited reporting of proprietary data by some established laboratories. Recent efforts to establish large public databases of genetic information (particularly ClinVar) will promote greater transparency and accountability and thus can help improve access to high quality care for hereditary conditions. Note: All of the variants in this study and their interpretations will be released to public databases by the time of the meeting. Citation Format: Stephen Lincoln, Allison Kurian, Andrea Desmond, Geoffrey Nilsen, Kevin Jacobs, Shan Yang, Reece Hart, Federico Monzon, Leif Ellisen, James Ford. Technical evaluation of multigene testing for hereditary breast and ovarian cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-12-07.

  PublisherDOI

• Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment

  JAMA Oncology · 2015-08-13 · 333 citations

  article1st authorCorresponding

  IMPORTANCE: The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown. OBJECTIVE: To define the potential clinical effect of multigene panel testing for HBOC in a clinically representative cohort. DESIGN, SETTING, AND PARTICIPANTS: Observational study of patients seen between 2001 and 2014 in 3 large academic medical centers. We prospectively enrolled 1046 individuals who were appropriate candidates for HBOC evaluation and who lacked BRCA1/2 mutations. INTERVENTIONS: We carried out multigene panel testing on all participants, then determined the clinical actionability, if any, of finding non-BRCA1/2 mutations in these and additional comparable individuals. MAIN OUTCOMES AND MEASURES: We evaluated the likelihood of (1) a posttest management change and (2) an indication for additional familial testing, considering gene-specific consensus management guidelines, gene-associated cancer risks, and personal and family history. RESULTS: Among 1046 study participants, 40 BRCA1/2-negative patients (3.8%; 95% CI, 2.8%-5.2%) harbored deleterious mutations, most commonly in moderate-risk breast and ovarian cancer genes (CHEK2, ATM, and PALB2) and Lynch syndrome genes. Among these and an additional 23 mutation-positive individuals enrolled from our clinics, most of the mutations (92%) were consistent with the spectrum of cancer(s) observed in the patient or family, suggesting that these results are clinically significant. Among all 63 mutation-positive patients, additional disease-specific screening and/or prevention measures beyond those based on personal and family history alone would be considered for most (33 [52%] of 63; 95% CI, 40.3%-64.2%). Furthermore, additional familial testing would be considered for those with first-degree relatives (42 [72%] of 58; 95% CI, 59.8%-82.2%) based on potential management changes for mutation-positive relatives. This clinical effect was not restricted to a few of the tested genes because most identified genes could change clinical management for some patients. CONCLUSIONS AND RELEVANCE: In a clinically representative cohort, multigene panel testing for HBOC risk assessment yielded findings likely to change clinical management for substantially more patients than does BRCA1/2 testing alone. Multigene testing in this setting is likely to alter near-term cancer risk assessment and management recommendations for mutation-affected individuals across a broad spectrum of cancer predisposition genes.

  PublisherDOI

• Ubiquitous Brms1 expression is critical for mammary carcinoma metastasis suppression via promotion of apoptosis Leah M. CookXuemei CaoAlexander E. DowellMichael T. Debies • Mick D. EdmondsBenjamin H. BeckRobert A. KestersonRenee A. Desmond • Andra R. FrostDouglas R. HurstDanny R. Welch

  2012-01-01

  article

  Morbidity and mortality of breast cancer patients are drastically increased when primary tumor cells are able to spread to distant sites and proliferate to become secondary lesions. Effective treatment of metastatic disease has been limited; therefore, an increased molecular under- standing to identify biomarkers and therapeutic targets is needed. Breast cancer metastasis suppressor 1 (BRMS1) suppresses development of pulmonary metastases when expressed in a variety of cancer types, including metastatic mammary carcinoma. Little is known of Brms1 function throughout the initiation and progression of mammary carcinoma. The goal of this study was to investigate mechanisms of Brms1-mediated metastasis suppression in transgenic mice that express Brms1 using polyoma middle T oncogene-induced models. Brms1 expression did not significantly alter growth of the primary tumors. When expressed ubiquitously using a b-actin promoter, Brms1 suppressed pulmonary metastasis and promoted apoptosis of tumor cells located in the lungs but not in the mammary glands. Surprisingly, selective expression of Brms1 in the mammary gland using the MMTV promoter did not sig- nificantly block metastasis nor did it promote apoptosis in the mammary glands or lung, despite MMTV-induced expression within the lungs. These results strongly suggest that cell type-specific over-expression of Brms1 is impor- tant for Brms1-mediated metastasis suppression.

  Publisher

Frequent coauthors

• Srinivas Vinod Saladi

  30 shared

• Kenneth N. Ross

  30 shared

• Sridhar Ramaswamy

  30 shared

• Michael S. Lawrence

  30 shared

• Leif W. Ellisen

  Massachusetts General Hospital

  25 shared

• Mihriban Karaayvaz

  18 shared

• Elena Zarcaro

  Center for Cancer Research

  18 shared

• Adam Langenbucher

  18 shared