Lee W

Agency for Science, Technology and Research

OpenAlex Profile
2
Publications
10
h-index
(1,893 citations, 66 total works)

Research Topics

Photonic and Optical Devices (11)Semiconductor Lasers and Optical Devices (8)Thyroid Cancer Diagnosis and Treatment (7)3D IC and TSV technologies (4)Nanofabrication and Lithography Techniques (4)

Alpha-gal Syndrome Publications

A Rare Case of Persistent Multifocal Cribriform-Morular Thyroid Carcinoma.

Kuenstner W, Zhao P, Lee W, Garcia C, Burman KD, et al.
AACE clinical case reports •

Cribriform-morular thyroid carcinoma (CMTC) was considered a variant of papillary thyroid carcinoma (PTC) but is a separate entity in the 2022 World Health Organization classification. CMTC has an association with familial adenomatous polyposis (FAP). Our objective is to report a case of CMTC who was subsequently diagnosed with FAP, to highlight these associated entities and implications for management. A 15-year-old female with a history of iron-deficiency anemia and alpha-gal syndrome presented with several years of goiter and dysphagia. She also noted unintentional weight loss, abdominal pain, melena and hematochezia, and symptomatic anemia. Physical examination was significant for multiple thyroid nodules. Laboratory results revealed normal thyroid function and iron deficiency. Multiple nodules were visualized on thyroid ultrasound, and fine needle aspiration biopsy was consistent with PTC. Total thyroidectomy was performed with a revised diagnosis of multifocal CMTC, with administration of adjuvant radioactive iodine due to persistent disease. Genetic testing confirmed FAP and she was referred for upper endoscopy, colonoscopy, and an evaluation for colectomy. There are no best practice guidelines for management of CMTC. Management of CMTC is guided by FAP status; sporadic cases can be managed with hemithyroidectomy, while FAP-associated cases are better managed with total thyroidectomy. Recurrence is usually managed with surgical resection. The decision to treat with adjuvant radioactive iodine is often extrapolated from management of classic PTC. Thyroid carcinoma in the setting of extensive family history of colorectal carcinoma should arouse suspicion for CMTC. Patients with CMTC should receive a referral for colonoscopy and genetic testing for FAP.

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Engineering an Enhanced EGFR Engager: Humanization of Cetuximab for Improved Developability.

Goulet DR, Chatterjee S, Lee WP, Waight AB, Zhu Y, et al.
Antibodies (Basel, Switzerland) •

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase whose proliferative effects can contribute to the development of many types of solid tumors when overexpressed. For this reason, EGFR inhibitors such as cetuximab can play an important role in treating cancers such as colorectal cancer and head and neck cancer. Cetuximab is a chimeric monoclonal antibody containing mouse variable regions that bind to EGFR and prevent it from signaling. Although cetuximab has been used clinically since 2004 to successfully control solid tumors, advances in protein engineering have created the opportunity to address some of its shortcomings. In particular, the presence of mouse sequences could contribute to immunogenicity in the form of anti-cetuximab antibodies, and an occupied glycosylation site in FR3 can contribute to hypersensitivity reactions and product heterogeneity. Using simple framework graft or sequence-/structure-guided approaches, cetuximab was humanized onto 11 new frameworks. In addition to increasing humanness and removing the VH glycosylation site, dynamic light scattering revealed increases in stability, and bio-layer interferometry confirmed minimal changes in binding affinity, with patterns emerging across the humanization method. This work demonstrates the potential to improve the biophysical and clinical properties of first-generation protein therapeutics and highlights the advantages of computationally guided engineering.

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